Pyrazolinone derivatives

ABSTRACT

The pyrazolinone derivatives represented by the formula [I]:                    
     [wherein R 1 , R 2 , R 3 , R 4  and R 5  may be identical or different and represent independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyl group, etc.; R 6  represents an optionally substituted alkyl group, etc.; X represents an optionally substituted alkyl group, etc,; and Y represents an oxygen atom or a sulfur atom] are provided.

This application is the national phase under 35 U.S.C. §371 of PCT International Application No. PCT/JP99/02147 which has an International filing date of Apr. 22, 1999, which designated the United States of America.

TECHNICAL FIELD

The present invention relates to the pyrazolinone derivatives, their uses and intermediate products.

BACKGROUND ART

The present invention aims at providing the compounds having an excellent plant disease controlling agent.

DETAILED DESCRIPTION OF THE INVENTION

As a result of extensive studies on the subject matter, the present inventors found that the pyrazolinone derivatives represented by the following formula [1] have an excellent controlling effect against plant diseases, and attained the present invention on the basis of this finding.

The present invention provides the pyrazolinone derivatives (hereinafter referred to as the present compounds) represented by the formula [I]:

[wherein R¹, R², R³, R⁴ and R⁵ may be identical or different and represent independently an hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, an alkoxyalkyl group, an alkoxyalkoxy group, a haloalkoxy group, an alkylthio group, a haloalkylthio group, a cyano group, a nitro group, an optionally substituted phenyl group or an optionally substituted phenoxyl group, or

adjacent two of R¹, R², R³, R⁴ and R⁵ are combined at the ends to represent a group of the formula CH═CH—CH═CH, a methylenedioxy group which may be substituted with a halogen atom, or an alkylene group which may contain one oxygen atom and may be substituted with an alkyl group;

R⁶ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group, or an optionally substituted alicyclic hydrocarbon group;

X represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group, an optionally substituted group, an optionally substituted alkenyloxy group, an optionally substituted alkynyloxy group, an optionally substituted phenoxyl group, an optionally substituted alkylthio group, an optionally substituted alkenylthio group, an optionally substituted alkynylthio group, an optionally substituted phenylthio group, or an optionally substituted alicyclic hydrocarbon group; and

Y represents an oxygen atom or a sulfur atom] and the plant disease controlling agents containing the present compound as an active ingredient.

The present invention further provides the pyrazolinone compounds represented by the following formula [II] which are useful as the intermediates for the preparation of the present compounds (these pyrazolinone compounds being hereinafter referred to as intermediates A):

[wherein R¹¹, R²¹, R³¹, R⁴¹ and R⁵¹ may be identical or different and represent independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, an alkoxyalkyl group, an alkoxyalkoxy group, a haloalkoxy group, an alkylthio group, a haloalkylthio group, a cyano group, a nitro group, an optionally substituted phenyl group or an optionally substituted phenoxyl group; or

adjacent two of R¹¹, R²¹, R³¹, R⁴¹ and R⁵¹ are combined at the ends to represent a group of the formula CH═CH—CH═CH, a methylenedioxy group which may be substituted with a halogen atom, or an alkylene group which may contain one oxygen atom and may be substituted with an alkyl group; and

R⁶¹ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group or an optionally substituted alicyclic hydrocarbon group]

and the pyrazolinone compounds represented by the formula [III] which are also useful as the intermediates for the preparation of the present compounds (these pyrazolinone compounds being hereinafter referred to as intermediates B):

[wherein R¹², R²², R³², R⁴² and R⁵² may be identical or different and represent independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxy group, an alkoxyalkyl group, an alkoxyalkoxy group, a haloalkoxy group, an alkylthio group, a haloalkylthio group, a cyano group, a nitro group, an optionally substituted phenyl group or an optionally substituted phenoxyl group, or

adjacent two of R¹², R²², R³², R⁴² and R⁵² are combined at the ends and represent a group of the formula CH═CH—CH═CH, a methylenedioxy group which may be substituted with a halogen atom, or an alkylene group which may contain one oxygen atom and may be substituted with an alkyl group;

X¹ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group, an optionally substituted alkoxy group, an optionally substituted alkenyloxy group, an optionally substituted alkynyloxy group, an optionally substituted phenoxyl group, an optionally substituted alkylthio group, an optionally substituted alkenylthio group, an optionally substituted alkynylthio group, an optionally substituted phenylthio group, or an optionally substituted alicyclic hydrocarbon group; and

Y¹ represents an oxygen atom or a sulfur atom].

MODES FOR CARRYING OUT THE INVENTION

In the present invention, the halogen atoms represented by R¹, R², R³, R⁴, R⁵, R¹¹, R²¹, R³¹, R⁴¹, R⁵¹, R¹², R²², R³², R⁴² and R⁵² in the formulae [I] to [III] include fluorine, chlorine, bromine and iodine.

The alkyl groups include C1-C5 alkyl groups such as methyl, ethyl, n-propyl, isopropyl, tert-butyl and n-pentyl.

The haloalkyl groups include C1-C5 haloalkyl groups such as trifluoromethyl, tetrafluoroethyl and heptafluoropropyl.

The alkoxy groups include C1-C5 alkoxy groups such as methoxy, ethoxy, normal propyloxy, isopropyloxy, n-butoxy and n-pentyloxy.

The alkoxyalkyl groups include C1-C3 alkoxy C1-C3 alkyl groups such as methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl and ethoxypropyl.

The alkoxyalkoxy groups include C1-C3 alkoxy C1-C3 alkoxy groups such as methoxymethoxy, methoxyethoxy, methoxypropoxy, ethoxymethoxy, ethoxyethoxy and ethoxypropoxy.

The haloalkoxy groups include C1-C5 haloalkoxy groups such as trifluoromethoxy, difluoromethoxy and tetrafluoroethoxy.

The alkylthio groups include C1-C5 alkylthio groups such as methylthio, ethylthio, n-propylthio, n-butylthio and n-pentylthio.

The haloalkylthio groups include C1-C5 haloalkylthio groups such as trifluoromethylthio.

The optionally substituted phenyl and phenoxyl groups include those which may be substituted with at least one group selected from halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxy groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxy groups, C1-C5 haloalkylthio groups and cyano groups.

Examples of the above-mentioned substituents are shown below:

Halogen atoms: fluorine, chlorine, bromine and iodine;

C1-C5 alkyl groups: methyl, ethyl, n-propyl, isopropyl, n-butyl and n-pentyl;

C1-C5 alkoxy groups: methoxy and ethoxy;

C1-C5 alkylthio groups: methylthio and ethylthio;

C1-C5 haloalkyl groups, preferably C1-C2 haloalkyl groups: trifluoromethyl;

C1-C5 haloalkoxy groups, preferably C1-C2 haloalkoxy groups: trifluoromethoxy and difluoromethoxy;

C1-C5 haloalkylthio groups, preferably C1-C2 haloalkylthio groups: trifluoromethylthio; and

Cyano groups.

Referring to the above R's, adjacent two of R¹ to R⁵, R¹¹ to R⁵¹, and R¹² to R⁵³ may be combined at the ends to form a methylenedioxy group which may be substituted with a halogen atom, such as difluoromethylenedioxy, or an alkylene group (such as C1-C6 alkylene group) which may contain an oxygen atom and may be substituted with an alkyl group (e.g. C1-C4 alkyl group), such as trimethylene, tetramethylene, a group of the formula OCH₂CH₂ or a group of the formula OCH₂CH(CH₃).

In the present compounds in view of the controlling effect against plant diseases, it is desirable that 1 to 3 substituents selected from R¹ to R⁵ is a halogen atom (especially chlorine), a haloalkyl group (especially trifluoromethyl) or an alkyl group (especially methyl), and the remainder of the substituents are a hydrogen atom. In view of the efficacy against Botrytis cinerea, it is desirable that R³, R⁴ and R⁵ are a hydrogen atom.

Examples of the optionally substituted alkyl groups represented by R⁶ and R⁶¹ in the present invention include the following:

C1-C10 alkyl groups such as ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 1-methylbutyl and 1-ethylpropyl;

C1-C10 haloalkyl groups such as 1-methyl-2,2,2-trifluoroethyl and 1-methyl-3-chloropropyl;

C1-C5 alkoxy C1-C5 alkyl groups such as 2-methoxyethyl;

C1-C5 alkylthio C1-C5 alkyl groups such as 2-methylthioethyl;

C1-C5 haloalkoxy C1-C5 alkyl groups such as 1-methyl-(2,2,2-trifluoroethoxy)ethyl;

C1-C5 haloalkoxy C1-C5 haloalkyl groups;

C1-C5 haloalkylthio C1-C5 alkyl groups such as 1-methyl-(2,2,2-trifluoroethylthio)ethyl;

C1-C5 haloalkylthio C1-C5 haloalkyl groups;

Cyano C1-C5 alkyl groups such as 1-cyanoethyl;

Cyano C1-C5 haloalkyl groups such as 1-cyano-2,2,2-trifluoroethyl;

C1-C5 alkoxycarbonyl C1-C5 alkyl groups such as 1-(methoxycarbonyl)ethyl; and

C1-C5 alkyl groups substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, such as 1-cyclopropyethyl.

Examples of the optionally substituted alkenyl groups represented by R⁶ and R⁶¹ include:

C3-C10 alkenyl groups such as 1-methyl-2-propenyl; and

C3-C10 haloalkenyl groups.

Examples of the optionally substituted alkynyl groups include:

C3-C10 alkynyl groups such as 1-methyl-2-propynyl, and C3-C10 aloalkynyl groups.

Examples of the optionally substituted alicyclic hydrocarbon groups include:

C3-C8 alicyclic hydrocarbon groups;

C3-C8 alicyclic hydrocarbon groups which may be substituted with a halogen atom and may contain unsaturated bonds, such as cyclopentyl and cyclohexyl; and

Phenyl groups and C7-C17 aralkyl groups which may be substituted with at least one group selected from halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups and C1-C5 haloalkylthio groups and cyano group, such as benzyl, α-methylbenzyl and α,α-dimethylbenzyl.

Examples of the optionally substituted alkyl groups represented by X or X¹ in the present invention include:

C1-C10 alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, 2-methylbutyl, isopentyl and tertiary butyl;

C1-C10 haloalkyl groups such as trifluoromethyl, tetrafluoroethyl, 2-chloroethyl, 3-chloropropyl and 4-chlorobutyl;

C1-C5 alkoxy C1-C5 alkyl groups such as methoxymethyl and 2-methoxyethyl;

C1-C5 alkylthio C1-C5 alkyl groups such as methylthiomethyl and 2-methylthioethyl;

C1-C5 haloalkoxy C1-C5 alkyl groups such as 2,2,2-trifluoroethoxymethyl;

C1-C5 haloalkoxy C1-C5 haloalkyl groups;

C1-C5 haloalkylthio C1-C5 alkyl groups such as 2,2,2-trifluoroethylthiomethyl;

C1-C5 haloalkylthio C1-C5 haloalkyl groups;

Cyano C1-C5 alkyl groups such as cyanomethyl, 1-cyanoethyl and 2-cyanoethyl;

Cyano C1-C5 haloalkyl groups; and

C1-C5 alkoxycarbonyl C1-C5 alkyl groups such as 1-(methoxycarbonyl)ethyl.

Examples of the optionally substituted aralkyl groups include C7-C17 aralkyl groups which may be substituted with at least one group selected from halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups, such as benzyl, α-methylbenzyl and α,α-dimethylbenzyl; and

C1-C5 alkyl groups substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, such as cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl.

Examples of the optionally substituted alkenyl groups include C2-C10 alkenyl groups such as vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl and 3-butenyl; and

C2-C10 haloalkenyl groups such as 3,3,3-trifluoropropenyl, and 1,1,2,3,3-pentafluoro-2-propenyl.

Examples of the optionally substituted alkynyl groups include C2-C10 alkynyl groups such as ethynyl, propalgyl, 2-butynyl and 3-butynyl; and C2-C10 haloalkynyl groups such as 3,3,3-tetrafluoropropynyl.

Examples of the optionally substituted alkoxyl groups include C1-C10 alkoxyl groups such as methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, isobutoxy, 2-methylbutoxy and isopentyloxy;

C1-C10 haloalkoxyl groups such as trifluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, tetrafluoropropoxy, 2-chloroetoxy, 3-chloropropoxy and 4-chlorobutoxy;

C1-C5 alkoxy C1-C5 alkoxyl groups such as 2-methoxyethoxy;

C1-C5 alkylthio C1-C5 alkoxyl groups such as 2-methylthioethoxy;

C1-C5 haloalkoxy C1-C5 alkoxyl groups such as 2,2,2-trifluoroethoxymethoxy;

C1-C5 haloalkoxy C1-C5 haloalkoxyl groups;

C1-C5 haloalkylthio C1-C5 alkoxyl groups such as 2,2,2-trifluoroethylthiomethoxy;

C1-C5 haloalkylthio C1-C5 haloalkoxyl groups;

Cyano C1-C5 alkoxyl groups such as 2-cyanoethoxy;

C1-C5 alkoxycarbonyl C1-C5 alkoxyl groups such as 2-(methoxycarbonyl)ethoxyl;

C1-C5 alkoxyl groups substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, such as cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy and cyclohexylmethoxy.

Examples of the optionally substituted alkenyloxy groups include C2-C10 alkenyloxy groups such as 2-propenyloxy, 2-butenyloxy and 3-butenyloxy; and

C2-C10 haloalkenyloxy groups such as 2,3,3-trifluoro-2-propenyloxy, 4,4,4-trifluoro-2-butenyloxy, 2,3-difluoro-2-butenyloxy, and 2,4,4,4-trifluoro-2-butenyloxy.

Examples of the optionally substituted alkynyloxy groups include C2-C10 alkynyloxy groups such as 2-propynyloxy, 2-butynyloxy, and 3-butynyloxy; and

C2-C10 haloalkynyloxy groups such as 4-chloro-2-butynyloxy.

Examples of the optionally substituted alkylthio groups include C1-C10 alkylthio groups such as methylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio, isobutylthio, 2-methylbutylthio and isopentylthio;

C1-C10 haloalkylthio groups such as trifluoroethylthio, tetrafluoroethylthio, pentafluoroethylthio, tetrafluoropropylthio, 2-chloroethylthio, 3-chloropropylthio, and 4-chlorobutylthio;

C1-C5 alkoxy C1-C5 alkylthio groups such as 2-methoxyethylthio:

C1-C5 alkylthio C1-C5 alkylthio groups such as 2-methylthioethylthio;

C1-C5 haloalkoxy C1-C5 alkylthio groups such as 2,2,2-tetrafluoroethoxymethylthio;

C1-C5 haloalkoxy C1-C5 haloalkylthio groups;

C1-C5 haloalkylthio C1-C5 alkylthio groups such as 2,2,2-tetrafluoroethylthiomethylthio:

C1-C5 haloalkylthio C1-C5 haloalkylthio groups;

Cyano C1-C5 alkylthio groups such as 2-cyanoethylthio;

C1-C5 alkoxycarbonyl C1-C5 alkylthio groups such as 2-(methoxycarbonyl)ethylthio;

C1-C5 alkylthio groups substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, such as cyclopropylmethylthio, cyclobutylmethylthio, cyclopentylmethylthio, cyclohexylmethylthio, (1-cyclopentenyl)methylthio, and (1-cyclohexenyl)methylthio.

Examples of the optionally substituted alkenylthio groups include C2-C10 alkenylthio groups such as 2-propenylthio, 2-butenylthio and 3-butenylthio;

C2-C10 haloalkenylthio groups such as 2,3,3-tetrafluoro-2-propenylthio, 4,4,4-tetrafluoro-2-butenylthio, 2,3-difluoro-2-butenylthio and 2,4,4,4-tetrafluoro-2-butenylthio.

Examples of the optionally substituted alkynylthio groups include C2-C10 alkynylthio groups such as 2-propynylthio, 2-butenylthio and 3-butenylthio; and C2-C10 haloalkynylthio groups.

Examples of the optionally substituted alicyclic hydrocarbon groups include C3-C8 alicyclic hydrocarbon groups which may be substituted with a halogen atom and may contain unsaturated bonds, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, 1,3-cyclopentadienyl, 2,4-cyclopentadienyl, 1-cyclohexenyl, 2-cyclohexenyl and 3-cyclohexenyl.

Examples of the optionally substituted phenyl groups, phenoxyl groups, C7-C17 aralkyloxy groups, C7-C17 aralkylthio groups and phenylthio groups include the phenyl groups, phenoxyl groups, C7-C17 aralkyl groups (such as benzyl, α-methylbenzyl and α,α-dimethylbenzyl), C7-C17 aralkyloxy groups and C7-C17 aralkylthio groups (such as benzylthio) which may be substituted with at least one group selected from halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano group.

Examples of the substituents include:

halogen atoms such as fluorine, chlorine, bromine and iodine;

C1-C5 alkyl groups such as methyl, ethyl, n-propyl, i-propyl, n-butyl and n-pentyl;

C1-C5 alkoxyl groups such as methoxy and ethoxy;

C1-C5 alkylthio groups such as methylthio and ethylthio;

C1-C5 haloalkyl groups, preferably C1-C2 haloalkyl groups such as trifluoromethyl;

C1-C5 haloalkoxyl groups, preferably C1-C2 haloalkoxyl groups such as trifluoromethoxy and difluoromethoxy;

C1-C5 haloalkylthio groups, preferably C1-C2 haloalkylthio groups such as trifluoromethylthio; and cyano groups.

In the present compounds in view of their efficacy for plant diseases, preferred examples of the substituents represented by X are C1-C5 alkyl groups, C1-C5 haloalkoxyl groups, C2-C5 alkenyloxy groups, C2-C5 haloalkenyloxy groups, C2-C5 alkynyloxy groups, C2-C5 haloalkynyloxy groups, C1-C5 alkylthio groups, C1-C5 haloalkylthio groups, C2-C5 alkenylthio groups, C2-C5 haloalkenylthio groups, C2-C5 alkynylthio groups and C2-C5 haloalkynylthio groups.

The present compounds can exist in the form of various tautomeric structures represented by the following formula [VII], and all of these tautomers are embraced within the concept of the present compounds.

Further, the present compounds may take the form of stereoisomers originating in the presence of double bonds and asymmetric carbon atoms, and these stereoisomers and their mixtures are also comprehended in the present compounds.

The intermediate A can exist in the form of various tautomeric structures represented by the following formula [VIII], and all of these tautomers are included in the intermediate A of the present invention.

The intermediate A may take the form of stereoisomers originating in the presence of double bonds and asymmetric carbon atoms, and these stereoisomers and their mixtures also fall within the ambit of the present compound.

The intermediate B can exist in the form of various tautomeric structures represented by the following formula [IX], and all of these tautomers are comprehended in the intermediate B of the present invention.

Further, in the intermediate B, there may exist the stereoisomers originating in the presence of double bonds and asymmetric carbon atoms, and these stereoisomers and their mixtures are also embraced in the concept of intermediate B according to the present invention.

The present compounds can be produced from the following processes.

(Process 1)

An alkaline metal salt of an intermediate A is reacted with a compound represented by the formula [X]:

[wherein X and Y are as defined previously, and Z represents a halogen atom (such as chlorine atom or bromine atom)] in an organic solvent.

The reaction is carried out at a temperature in the range of usually 80 to 140° C. for a period of usually 0.1 to 5 hours, using a compound of the formula [X] usually in a ratio of 1 to 3 moles, preferably 1.1 to 2 moles to one mole of an alkaline metal salt of an intermediate A.

As the organic solvent in the above reaction, aromatic hydrocarbons such as toluene, xylene and chlorobenzene, ethers such as diethyl ether, 1,4-dioxane, tetrahydrofuran, tetrahydropyran, diisopropyl ether and dimethoxyethane, dimethylformamide, and mixtures thereof can be used. 1,4-dioxane or dimethoxyethane is preferably used.

After the completion of the reaction, the reaction solution is poured into water and subjected to the ordinary after-treatments such as extraction with an organic solvent and concentration to give the present compound. The obtained compound can be purified by suitable means such as washing with an organic solvent, recrystallization and column chromatography.

An alkaline metal salt of an intermediate A can be produced by reacting an intermediate A with sodium hydroxide, anhydrous lithium hydroxide or a lithium hydroxide monohydrate under an azeotropic dehydrating condition, or by reacting an intermediate A with sodium hydride or lithium hydride.

In case of reacting an intermediate A with sodium hydroxide, anhydrous lithium hydroxide or a lithium hydroxide monohydrate under an azeotropic dehydrating condition, the reaction is carried out usually at 80 to 140° C. for usually 0.5 to 12 hours by supplying usually 1 to 5 moles, preferably 1.1 to 2 moles of sodium hydroxide, anhydrous lithium hydroxide or a lithium hydroxide monohydrate to one mole of an intermediate A, using, for example, an aromatic hydrocarbon such as toluene, xylene or chlorobenzene as the reaction solvent.

In case of reacting an intermediate A with sodium hydride or lithium hydride, the reaction is conducted usually at 60 to 120° C. for a period of usually 1 to 12 hours by supplying 1 to 2 moles of sodium hydride or lithium hydride to one mole of an intermediate A, using, for example, an aromatic hydrocarbon such as toluene, xylene or chlorobenzene, an ether such as diethyl ether, 1,4-dioxane, tetrahydrofuran, tetrahydropyran, diisopropyl ether or dimethoxyethane, or dimethylformamlde, preferably 1,4-dioxane or dimethoxyethane as the reaction solvent.

After the completion of the reaction, the solvent in the reaction solution is distilled off under reduced pressure to form an alkaline metal salt of an intermediate A.

The compounds represented by the formula [X] can be produced, for instance, according to the methods described in Org. Syn. 1, 147; J. Am. Chem. Soc. 73, 3796 (1951); J. Am. Chem. Soc. 81, 714 (1959); Angew. Chem. Int. Ed. Engl., 26, 894 (1987); and Synthesis, 760 (1986).

The intermediates A can be produced by acting an acid catalyst to the pyrazolinone derivatives represented by the formula [XI]:

[wherein R¹¹, R²¹, R³¹, R⁴¹, R⁵¹ and R⁶¹ are as defined previously].

The reaction is carried out usually at a temperature in the range of 80 to 120° C. for a period of usually 1 to 12 hours by supplying usually 0.1 mole to an excess amount of an acid to one mole of a pyrazolinone derivative of the formula [XI].

As the acid in the above reaction, there can be used, for example, mineral acids such as hydrochloric acid and sulfuric acid in the form of an aqueous solution.

As the solvent, the above-mentioned acids, alcohols such as methanol and ethanol, their mixtures, etc., can be used.

After the completion of the reaction, the reaction solution may be neutralized with a basic aqueous solution such as a sodium hydroxide solution or a sodium hydrogencarbonate solution, then concentrated and washed with water to produce an intermediate A. The obtained compound can be purified by suitable means such as washing with an organic solvent, recrystallization, column chromatography, etc.

The pyrazolinone derivatives represented by the formula [XI] can be produced according to the method described in JP-A-8-208621.

(Process 2)

An alkaline metal salt of an intermediate B is reacted with a compound represented by the formula [XII]:

R⁶—L

[wherein R⁶ is as defined above, and L represents a chlorine atom, a bromine atom, an iodine atom, a C1-C10 alkanesulfonyloxy group or an optionally substituted benzenesulfonyloxy group] in an organic solvent.

The reaction is carried out usually at a temperature in the range of 60 to 150° C., preferably 80° to 120° C. for a period of usually 0.1 to 12 hours by supplying usually 1 to 5 moles, preferably 1 to 2.5 moles of a compound of the formula [XI] to one mole of an alkaline metal salt of an intermediate B.

The organic solvents usable for the above reaction include aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbons such as normal hexane and normal heptane, ethers such as tetrahydrofuran, 1,4-dioxane and tetrahydropyran, and their mixtures.

After the completion of the reaction, the reaction solution is poured into acidic water and then subjected to the ordinary after-treatments such as extraction with an organic solvent, concentration, etc., to produce the present compound. The obtained compound can be purified by suitable means such as washing with an organic solvent, recrystallization, column chromatography, etc.

An alkaline metal salt of an intermediate B can be produced by reacting an intermediate B with sodium hydroxide, anhydrous lithium hydroxide or a lithium hydroxide monohydrate under an azeotropic dehydrating condition, or by reacting an intermediate B with sodium hydride or lithium hydride.

In case of reacting an intermediate B with sodium hydroxide, anhydrous lithium hydroxide or a lithium hydroxide monohydrate under an azeotropic dehydrating condition, the reaction is carried out usually at 80 to 140° C. for usually 0.5 to 12 hours by supplying usually 1 to 5 moles, preferably 1.1 to 2 moles of sodium hydroxide, anhydrous lithium hydroxide or a lithium hydroxide monohydrate to one mole of an intermediate B using, for instance, an aromatic hydrocarbon such as toluene, xylene or chlorobenzene as the reaction solvent.

In case of reacting an intermediate B with sodium hydride or lithium hydride, the reaction is carried out usually at 60 to 120° C. for usually 1 to 12 hours by supplying 1 to 2 moles of sodium hydride or lithium hydride to one mole of an intermediate B, using an aromatic hydrocarbon such as toluene, xylene or chlorobenzene, an ether such as diethyl ether, 1,4-dioxane, tetrahydrofuran, tetrahydropyran, diisopropyl ether or dimethoxyethane, dimethylformamide or the like, preferably 1,4-dioxane or dimethoxyethane as the reaction solvent.

The intermediates B can be produced, for example, by the following processes.

{Preparation Process 1 of the Intermediate}

A pyrazolinone compound represented by the formula [V′]:

[wherein R¹², R²², R³², R⁴² and R⁵² are as defined above] is reacted with a compound represented by the formula [XIII]:

[wherein X¹ and Y¹ are as defined above, and Z¹ represents a halogen atom (such as chlorine atom or bromine atom)] in an organic solvent in the presence of a base.

The reaction is carried out usually at a temperature in the range of 0 to 100° C., preferably 10 to 50° C., for a period of usually 1 to 12 hours by supplying usually 0.8 to 1.2 mole, preferably 1 to 1.1 mole of a compound of the formula [XIII] to one mole of a pyrazolinone compound of the formula [V′]. A base is used in a ratio of usually 1 to 5 moles, preferably 1 to 1.5 mole.

As the base, there can be used inorganic bases, for example, alkaline metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, alkaline metal or alkaline earth metal carbonates such as sodium carbonate, potassium carbonate, magnesium carbonate and calcium carbonate, and alkaline metal bicarbonates such as sodium bicarbonate and potassium bicarbonate, and organic bases such as pyridine, N,N-dimethylpyridine and triethylamine. In case of using an inorganic base, it may be applied as an aqueous solution.

As the solvent, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbons such as normal hexane and normal heptane, ketones such as methyl ethyl ketone and methyl isobutyl ketone, ethers such as tetrahydrofuran, 1,4-dioxane and tetrahydropyran, and their mixtures can be used. Water may be allowed to co-exist with an organic solvent, in which case water and the organic solvent may stay homogeneous or heterogeneous.

After the completion of the reaction, the reaction solution is poured into acidic water and subjected to the ordinary after-treatments such as extraction with an organic solvent, concentration of the organic layer, etc., to obtain an intermediate B. The obtained compound may be purified by suitable means such as washing with an organic solvent, recrystallization, column chromatography, etc.

The pyrazolinone derivatives represented by the formula [V′] can be produced, for example, according to the method described in J. Chem. Soc. Chem. Commum., 23, 1755-1757 (1993).

The compounds represented by the formula [XIII] can be produced according to the methods described in Org. Syn. 1, 147; J. Am. Chem. Soc. 73, 3796 (1951); J. Am. Chem. Soc., 81, 714 (1959); Angew. Chem. Int. Ed. Engl., 26, 984 (1987); Synthesis, 760 (1986), etc.

{Preparation Process 2 of the Intermediate}

A pyrazolinone compound represented by the formula [V′] is reacted with a compound represented by the formula [XIV]:

Z²—G

[wherein G represents a C1-C5 trialkylsilyl group such as trimethylsilyl, treithylsilyl, dimethylethylsilyl, dimethylisopropyl or tert-butyldimethylsilyl, and Z² represents a halogen atom such as chlorine, bromine or iodine] in an organic solvent in the presence of a base, then further reacted with a compound represented by the formula [XIII], and subjected to the after-treatments in acidic water.

The reaction is carried out usually at a temperature in the range of 0 to 100° C., preferably 0 to 30° C. for a period of usually 1 to 12 hours by supplying usually 1 to 1.5 mole, preferably 1 to 1.2 mole of a compound of the formula [XIV] and a compound of the formula [XIII] to one mole of a pyrazolinone compound of the formula [V′] . The ratio of the base used in the reaction is usually 2 to 10 moles, preferably 2 to 5 moles.

As the base, organic bases such as pyridine and triethylamine can be used.

As the solvent, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbons such as normal hexane and normal heptane, ketones such as methyl ethyl ketone and methyl isobutyl ketone, ethers such as tetrahydrofuran, 1,4-dioxane and tetrahydropyran, and their mixtures can be used.

After the completion of the reaction, the reaction solution is poured into acidic water, or if necessary the reaction solution is filtered to remove the precipitate and the filtrate is poured into acidic water, then stirred under reflux for 0.5 to 5 hours, preferably 0.5 to 2 hours, extracted with an organic solvent, and subjected to the after-treatments such as concentration of the organic layer to give a pyrazolinone compound of the formula [VI]. The obtained compound can be purified by suitable means such as washing with an organic solvent, recrystallization, column chromatography, etc.

(Process 3)

An intermediate B and a compound represented by the formula [XII] are reacted in an organic solvent in the presence of a base.

The reaction is carried out at a temperature in the range of usually 60 to 180° C., preferably 80 to 120° C. for a period of usually 1 to 12 hours by supplying usually 1 to 5 moles, preferably 1 to 2.5 moles of a compound of the formula [XI] to one mole of an alkaline metal salt of an intermediate B and allowing a base to exist in a ratio of usually 1 to 5 moles, preferably 1 to 2.5 moles.

As the base in the above reaction, organic bases, for example, alkaline metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide, alkaline metal or alkaline earth metal carbonates such as sodium carbonate, potassium carbonate, magnesium carbonate and calcium carbonate, alkaline metal bicarbonates such as sodium bicarbonate and potassium bicarbonate, pyridine, N-N-dimethylpyridine, triethylamine, etc., can be used.

As the organic solvent for the above reaction, aromatic hydrocarbons such as benzene, toluene, xylene and chlorobenzene, aliphatic hydrocarbons such as normal hexane and normal heptane, ethers such as tetrahydrofuran, 1,4-dioxane and tetrahydropyran, and their mixtures are usable.

If necessary, molecular sieves (synthetic zeolite) may be allowed to exist in the reaction system.

After the completion of the reaction, the reaction solution is poured into acidic water and subjected to the ordinary after-treatments such as extraction with an organic solvent, concentration, etc., to obtain the present compound. The obtained compound may be purified by suitable means such as washing with an organic solvent, recrystallization, column chromatography, etc.

When the present compound is used as an active ingredient of the plant diseases controlling agent, the compounds may be used as they are without adding any other components, but usually they are mixed with proper adjuvants such as solid carrier, liquid carrier, surfactant, etc., and formulated into a desired form of preparation such as emulsifiable concentrate, wettable powder, flowable, dust, granule, etc. In these formulations, the content of the present compound as an active ingredient is usually 0.1 to 99%, preferably 1 to 90% in ratio by weight.

Examples of the solid carriers usable in the formulations include fine powders or granules of kaolin clay, attapulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, corncob, walnut shell, urea, ammonium sulfate, synthetic hydrous silicon oxide and the like. Examples of the liquid carriers include aromatic hydrocarbons such as xylene and methyl naphthalene, alcohols such as isopropanol, ethylene glycol and cellosolve, ketones such as acetone, cyclohexanone and isophorone, plant oils such as soybean oil and cottonseed oil, dimethyl sulfoxide, acetonitrile and water.

Examples of the surfactants usable for the above formulations include anionic surfactants such as alkylsulfate ester salts, alkyl(aryl)sulfonates, dialkyl sulfosuccinate, polyoxyethylene alkylaryl ether phosphoric ester salts, naphthalenesulfonic acid-formalin condensate, etc., and nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene-alkylpolyoxypropene block copolymer, sorbitan fatty acid esters, etc.

Examples of the adjuvants usable for the above formulations include lignin sulfonate, alginates, polyvinyl alcohol, gum arabic, carboxymethyl cellulose (CMC), acidic isopropyl phosphate (PAP) and the like.

The present compound may be applied in folian application, soil treatment, seed disinfection and the like, and usually any application method which one skilled in the art employs may also be used.

When the present compound is used as an active ingredient for the plant disease controlling agent, the quantity of the compound (active ingredient) to be applied is usually 0.01 to 5 g/are, preferably 0.05 to 10 g/are, though it is variable depending on the type of the plant (crop, etc.) to be treated, type of the plant disease to be controlled, degree of affection by the disease, dosing form way of application, time of application, weather conditions, etc.

In case the compound is used in the form of an emulsifiable concentrate, wettable powder, flowable etc. by diluting it with water, the concentration of the compound in such aqueous formulations should be 0.0001 to 0.5%, preferably 0.0005 to 0.2%. When the compound is used as a dust or granule, it may be applied as it is without dilution.

The present compound can be used as a controlling agent against plant diseases in the plowed fields, paddy fields, orchards, tea plantations, pastures, lawns and the like. Also, an increased germicidal effect can be expected by using the compounds in admixture with other known plant disease controlling agents. Examples of such admixable other controlling agent include azole type germicidal compounds such as Propiconazole, Triadimenol, Prochloraz Penconazole, Tebuconazole, Flusilazole, Diniconazole, Bromconazole, Epoxyconazole, Diphenoconazole, Ciproconazole, Metoconaznole, Triflumizole, Tetraconazole, Microbutanil, Fenbuconal, Hexaconazole, Fluquinconazole, Triticonazole (RPA4007), Bitertanol, Imazalil, and Flutriafol, cyclic amine type germicidal compounds such as Fenpropimorph, Tridemorph and Fenpropidin, benzimidazole type germicidal compounds such as Carbendazim, Benonyl, Tiabendazole and Thiophanate-methyl, procymidone, Cyprodinil, Pyrimethanil, Diethofencarb, Thiuram, Fluazinam, Mancozeb, Iprodione, Vinclozolin, Chlorothalonil, Captan, Mapanipyrim, Fenpiclonil, Kresoximmethyl, Fludioxonil, Dichlofluanide, Folpet, Azoxystrobin, and N-methyl-α-methoxyimino-2-[(2,5-dimethylphenoxy)methyl]-phenylacetamide. Further, the compounds of the present invention can be used in admixture or combination with the known insecticides, miticides, nemacides, herbicides, plant growth regulators and fertilizers.

The present compound are effective for controlling a variety of plant diseases, for example, those mentioned below:

Pyricularia oryzae, Cochliobolus miyabeanus, Rhizoctonia solani, Erysiphe graminis, Gibberella zeae, Puccinia striiformis, P. graminis, P. recondita, P. hordei, Typhula sp., Micronectriella nivalis, Ustilago tritici, U. nuda, Tilletia caries, Pseudocercosporella herpotrichoides, Rhynchosporium secalis, Septoria tritici, Leptosphaeria nodorum, Diaporthe citri, Elsinoe fawcetti, Penicillium digitatum, P. italicum, Sclerotinia mali, Valsa mali, Pososphaera leucotricha, Alternaria mali, Venturia inaeqaulis, Venturia nashicola, V. pirina, Alternaria kikuchiana, Gymnosporangium haraeanum, Sclerotinia cinerea, Cladosporium carpophilum, Phomopsis sp., Elsinoe ampelina, Glomerella cingulata, Uncinula necator, Phakopsora ampelopsidis, Guignardia bidwellii, Plasmopara viticola, Gloeosporium kaki, Cercospora kaki, Mycosphaerella nawae, Colletotrichum lagenarium, Sphaerotheca fuliginea, Mycosphaerella melonis, Fusarium oxysporum, Pseudoperonospora cubensis, Phytophthora sp., Pythium sp., Alternaria solani, Cladosporium fulvum, Phytophthora inlestans, Phomopsis vexans, Erysiphe cichoracearum, Alternaria japonica, Cercosporella brassicae, Puccinia allii, Cercospora kikuchii, Elsinoe glycines, Diaporthe phaseolorum var. sojae, Colletotrichum lindemthianum, Cercospora personata, Cercospora arachidicola, Erysiphe pisi, Alternaria solani, Phytophthora infestans, Sphaerotheca humuli, Exobasidium reticulatum, Elsinoe leucospila, Alternaria longipes, Erysiphe cichoracearum, Colletorichum tabacum, Peronospora tabacina, Phytophthora nicotianae, Cercospora beticola, Diplocarpon rosae, Sphaerotheca pannosa, Septoria chrysanthemi indici, Puccinia horiana, Botrytis cinerea of various farm products, and Sclerotinia sclerotiorum.

EXAMPLES

The present invention is explained in more detail in the following Production Examples, Formulation Examples and Test Examples, but it should be understood that the scope of the present invention is not restricted to these Examples.

First, the production examples of the present compound, their intermediate A and intermediate B are described. In the following descriptions of the Examples, the compound numbers correspond to those shown in Tables 1 to 64 given below. The symbol “(+)-” or “(−)-” put in front of the compound number indicates that the compound is a single body of an optically active substance or a mixture of optically active substances and has a plus (+) or minus (−) specific rotation.

For the purity assay of the obtained objective products, liquid chromatographic analysis (hereinafter referred to as LC) was conducted under the following conditions.

<LC Conditions>

Analyzer: low pressure gradient type (Hitachi L-6000 Series)

Column: L-column ODS (4.6 mmφ×150 mm; mfd. by Kagakuhin Kensa Kyokai (Chemical Substances Testing Association)

Column temperature: 40° C.

Detector: UV (254 nm)

Mobile phase condition: gradient method (solution A & solution B)

Time (min): 0, 10, 35, 45

Solution B conc. (%): 50, 50, 100, 100

Flow rate (ml/min): 1.0 ml/min

(Solution A: 0.1% phosphoric acid/water; solution B: 0.1% phosphoric acid/acetonitrile)

Production Example 1

1.57 (5.5 mmol) of an intermediate A (Compound 1007) was suspended in 20 ml of dioxane, to which 0.30 g (7.5 mmol) of 60% oily sodium hydride was added, and the mixture was heated to 90° C. Then 0.72 g (7.6 mmol) of methyl chloroformate was added dropwise. After stirring at the same temperature for one hour, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with water and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and the obtained white solid was washed with a mixed solvent of ethyl acetate and hexane to obtain 0.13 mg (0.38 mmol) of the present compound (Compound 138).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.33 (1H) , 7.15-7.21 (2H), 5.74 (2H), 4.02 (1H), 3.96 (3H), 1.37 (6H).

Production Example 2

50 ml of toluene was added to a mixture of 5.00 g (17.5 mmol) of an intermediate A (Compound 1007) and 1.47 g (35.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, then 35 ml of 1,4-dioxane was added and further 4.22 g (35.0 mmol) of aryl chloroformate was added dropwise under reflux. After stirring for 15 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was extracted with ethyl acetate. The organic layer was washed twice with water and the solvent was distilled off under reduced pressure. A small quantity of a hexane/ethyl acetate mixed solvent was added to the residue, and the precipitated solids were filtered out and washed with a hexane/ethyl acetate mixed solvent to obtain 2.67 g (7.22 mmol) of the present compound (Compound 203) having a melting point of 173.8° C.

Production Example 3

20 ml of toluene was added to a mixture of 2.45 g (10.0 mmol) of an intermediate A (Compound 1017) and 0.84 g (20.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, then 20 ml of 1,4-dioxane was added and further 2.41 g (20.0 mmol) of allyl chloroformate was added dropwise under reflux. After stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was extracted with ethyl acetate. The organic layer was washed twice with water, then the solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.53 g (1.88 mmol) of the present compound (Compound 330) having a melting point of 102.1° C.

Production Example 4

1.57 g (5.5 mmol) of an intermediate A (Compound 1007) was dissolved in 5 ml of dimethylformamide, to which 0.30 g (7.5 mmol)of 60% oily sodium hydride was added under cooling with water, followed by dropwise addition of 0.65 g (5.99 mmol) of ethyl chloroformate under cooling with water. After stirring at room temperature for 30 minutes, the reaction solution was poured into water and extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure, and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 0.61 g (1.76 mmol) of the present compound (Compound 151).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.37 (1H), 7.18-7.23 (2H), 5.71 (2H), 4.42 (2H), 4.05 (1H), 1.40-1.47 (9H).

Production Example 5

0.98 g (3.44 mmol) of an intermediate A (Compound 1007) was dissolved in 5 ml of dimethylformamide, to which 0.15 g (3.75 mmol) of 60% oily sodium hydride was added under cooling with water and stirred for 30 minutes. Then 0.54 g (3.78 mmol) of 2-chloroethyl chloroformate was added dropwise under cooling with water. After stirring at room temperature for one hour, the reaction solution was poured into water and extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to provide 0.68 g (1.72 mmol) of the present compound (Compound 582).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.37 (1H), 7.19-7.24 (2H), 5.69 (2H), 4.60 (2H), 4.09 (1H), 3.84 (2H), 1.44 (6H).

Production Example 6

15 ml of toluene was added to a mixture of 2.00 g (6.99 mmol) of an intermediate A (Compound 1007) and 0.59 g (14 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, then 20 ml of 1,4-dioxane was added and further 1.91 g (14 mmol) of isobutyl chloroformate was added dropwise under reflux. After stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was washed with an ethyl acetate/hexane mixed solvent to obtain 1.0 g (2.59 mmol) of the present compound (Compound 190) having a melting point of 153.7° C.

Production Example 7

1.41 g (4.73 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 1.12 g (14.2 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 15 minutes, 0.79 g (14.1 mmol) of 2-propyne-1-ol was added dropwise, and after additional 35-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate A”.

20 ml of toluene was added to a mixture of 2.02 g (7.06 mmol) of an intermediate A (Compound 1007) and 0.59 g (14.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, then 15 ml of 1,4-dioxane was added and the previously obtained “filtrate A” was further added dropwise under reflux. After stirring for 5 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 0.53 g (1.44 mmol) of the present compound (Compound 229) having a melting point of 137.4° C.

Production Example 8

0.98 g (3.29 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 0.79 g (10.0 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 15 minutes, 0.56 g (10.0 mmol) of 2-propyne-1-ol was added dropwise, and after additional 15-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate B”.

20 ml of toluene was added to a mixture of 1.50 g (5.00 mmol) of an intermediate A (Compound 1020) and 0.42 g (10.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. After toluene was distilled off under reduced pressure, 10 ml of 1,4-dioxane was added and the previously prepared “filtrate B” was added dropwise under reflux. After stirring for one hour under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue, and the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.33 g (0.86 mmol) of the present compound (Compound 359) having a melting point of 132.7° C.

Production Example 9

1.40 g (4.67 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 1.11 g (14 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for one hour, 1.03 g (14 mmol) of cyclopropane methanol was added dropwise, and after additional 15-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate C”.

20 ml of toluene was added to a mixture of 2.0 g (7.00 mmol) of an intermediate A (Compound 1007) and 0.59 g (14.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for one hour while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, and 10 ml of 1,4-dioxane was added. Then the previously prepared filtrate C was added dropwise under reflux, and after stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure, and the residue was washed with an ether/hexane mixed solvent to obtain 0.80 g (2.08 mmol) of the present compound (Compound 578) having a melting point of 178.2° C.

Production Example 10

1.40 g (4.67 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 1.1 g (14 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 15 minutes, 1.03 g (14 mmol) of 3-butene-1-ol was added dropwise, and after additional 15-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate D”.

20 ml of toluene was added to a mixture of 2.0 g (7.00 mmol) of an intermediate A (Compound 1007) and 0.59 g (14.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for one hour while removing water by azeotropic dehydration. With toluene distilled off under reduced pressure, 10 ml of 1,4-dioxane was added and the filtrate D was added dropwise under reflux. After stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 0.65 g (1.84 mmol) of the present compound (Compound 216) having a melting point of 133.1° C.

Production Example 11

1.40 g (4.67 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 1.1 g (14 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 30 minutes, 0.98 g (14 mmol) of 1-butyne-1-ol was added dropwise, and after additional 15-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate E”.

20 ml of toluene was added to a mixture of 2.0 g (7.00 mmol) of an intermediate A (Compound 1007) and 0.59 g (14.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for one hour while removing water by azeotropic dehydration. After distilling off toluene under reduced pressure, 10 ml of 1,4-dioxane was added and the filtrate E was further added dropwise under reflux. After further stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue and the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 1.0 g (2.84 mmol) of the present compound (Compound 255) having a melting point of 152.0° C.

Production Example 12

1.41 g (4.67 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 1.1 g (14 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 15 minutes, 0.98 g (14 mmol) of 3-butyne-1-ol was added dropwise, and after additional one-hour stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate F”.

20 ml of toluene was added to a mixture of 2.0 g (7.00 mmol) of an intermediate A (Compound 1007) and 0.59 g (14.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for one hour while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, 10 ml of 1,4-dioxane was added, and the filtrate F was added dropwise under reflux. After stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue, the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 0.58 g (1.65 mmol) of the present compound (Compound 242) having a melting point of 160.3° C.

Production Example 13

0.98 g (3.29 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 0.79 g (10 mmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 25 minutes, 0.72 g (10 mmol) of 2-butene-1-ol was added dropwise, and after additional 15-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate G”.

10 ml of toluene was added to a mixture of 1.5 g (5.0 mmol) of an intermediate A (Compound 1020) and 0.42 g (10.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for one hour while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, then 10 ml of 1,4-dioxane was added, and the filtrate G was added dropwise under reflux. After further stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue, the resulting solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 0.47 g (1.18 mmol) of the present compound (Compound 346) having a melting point of 127.7° C.

Production Example 14

20 ml of toluene was added to a mixture of 1.43 g (5.0 mmol) of an intermediate A (Compound 1007) and 0.42 g (10.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, 20 ml of 1,4-dioxane was added, and further 1.1 ml (9.1 mmol) of S-ethyl chlorothioformate was added dropwise under reflux. After stirring for 10 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue, the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. The solvent was distilled off under reduced pressure and the residue was collected and subjected to thin layer chromatography to obtain 0.24 g (0.64 mmol) of the present compound (Compound 411) having a melting point of 177.5° C.

Production Example 15

0.98 g (3.29 mmol) of bis(trichloromethyl)carbonate was dissolved in 10 mml of 1,4-dioxane, to which 0.79 g (10.0 mmmol) of pyridine was added dropwise under cooling with water. After stirring at room temperature for 30 minutes, 1.35 g (10.0 mmol) of 55% 2-propene-1-thiol was added dropwise, and after additional 30-minute stirring at room temperature, the reaction solution was filtered to obtain a filtrate. This filtrate is called “filtrate H”.

20 ml of toluene was added to a mixture of 1.41 g (4.93 mmol) of an intermediate A (Compound 1007) and 0.42 g (10.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure and 10 ml of 1,4-dioxane was added. Then the filtrate H was added dropwise under reflux, and after additional 10-minute stirring under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue, the solution was extracted with ethyl acetate, and the organic layer was washed twice with water. Then the solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.14 g (0.36 mmol) of the present compound (Compound 463) of m.p. 170.8° C.

Production Example 16

10 ml of toluene was added to a mixture of 1.22 g (5.0 mmol) of an intermediate A (Compound 1017) and 0.42 g (10.0 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, 10 ml of 1,4-dioxane was added and then 1.25 g (10.0 mol) of S-ethyl chlorothioformate was further added dropwise under reflux. After stirring for 30 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure. Water was added to the residue, this solution was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.14 g (0.42 mmol) of the present compound (Compound 499) of m.p. 137.8° C.

Production Example 17

10 ml of toluene was added to a mixture of 1.20 g (4.9 mmol) of an intermediate A (Compound 1017) and 0.41 g (9.8 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for 30 minutes while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, 10 ml of 1,4-dioxane was added, and then 1.0 g (7.3 mmol) of S-allyl chlorothioformate was added dropwise under reflux. After stirring for 15 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with a saline solution. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.09 g (0.26 mmol) of the present compound (Compound 551) of m.p. 146.6° C.

Production Example 18

20 ml of toluene was added to a mixture of 2.2 g (7.7 mmol) of an intermediate A (Compound 1007) and 0.48 g (11.4 mmol) of lithium hydroxide monohydrate, and the mixture was refluxed for one hour while removing water by azeotropic dehydration. Toluene was distilled off under reduced pressure, 20 ml of 1,4-dioxane was added and then 1.46 g (11.7 mmol) of O-ethyl chlorothioformate was added dropwise under reflux. After stirring for 5 minutes under the refluxing condition, 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 0.11 g (0.29 mmol) of the present compound (Compound 621).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.38 (1H), 7.20-7.26 (2H), 6.45 (2H), 4.66 (2H). 3.94 (1H), 1.53 (3H), 1.43 (6H).

Production Example 19

60 mg (7.5 mmol) of lithium hydride was added to a solution of an intermediate B (Compound 2147) in a 1.39 g (5 mmol) of a dioxane and the mixture was refluxed for 10 minutes. Then 1.0 g (7.2 mmol) of isopropyl methanesulfonate was added and the mixture was further refluxed for 30 minutes. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to obtain 1.14 g (3.57 mmol) of the present compound (Compound 408).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.17-7.24 (4H), 5.5 (2H), 3.91 (1H), 2.95 (2H), 2.26 (3H), 1.43 (6H), 1.36 (3H).

Production Example 20

32 mg (4 mmol) of lithium hydride was added to a dioxane solution of 852 mg (3.08 mmol) of an intermediate B (Compound 2147) and the mixture was refluxed for 10 minutes. Then 570 mg (4.6 mmol) of ethyl methanesulfonate was added and the mixture was refluxed for one hour. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 230 mg (0.75 mmol) of the present compound (Compound 595).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.21-7.26 (4H), 5.7 (2H), 3.8 (2H), 2.98 (2H), 2.28 (3H), 1.38 (3H), 1.05 (3H).

Production Example 21

85 mg (10.6 mmol) of lithium hydride was added to a dioxane solution of 2.07 g (6.23 mmol) of an intermediate B (Compound 2150) and the mixture was refluxed for 10 minutes. Then 1.6 g (10.5 mmol) of secondary butyl methanesulfonate was added and the mixture was further refluxed for one hour. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 1.25 g (3.22 mmol) of the present compound (Compound 502).

¹H-NMR (CDCl₃, TMS) δ (ppm): 7.37 (1H), 7.18-7.26 (2H), 5.63 (2H), 3.63 (1H), 2.97 (2H), 1.88-2.09 (2H), 1.35-1.41 (6H), 1.00 (3H).

Production Example 22

95 mg (12 mmol) of lithium hydride was added to a dioxane solution of 2.0 g (7.2 mmol) of an intermediate B (Compound 2147) and the mixture was refluxed for 10 minutes. Then 1.8 g (11.8 mmol) of (−)-secondary butyl methanesulfonate {[α]¹⁸ _(D)=−1.42 (c=7, CHCl₃)} was added and the mixture was further refluxed for one hour. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 1.3 g (3.9 mmol) of the present compound (Compound (+)-499).

[α]¹⁸ _(D)=+0.422 (c=5.5, CHCl₃)

Production Example 23

90 mg (11.3 mmol) of lithium hydride was added to a dioxane solution of 1.93 g (7.0 mmol) of an intermediate B (Compound 2147) and the mixture was refluxed for 10 minutes. Then 1.7 g (11.1 mmol) of (+)-secondary butyl methanesulfonate {[α]¹⁸ _(D)=+1.49 (c=7, CHCl₃)} was added and the mixture was further refluxed for one hour. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 1.0 g (3.0 mmol) of the present compound (Compound (−)-499).

[α]¹⁸ _(D)=−0.389 (c=5.4, CHCl₃)

Production Example 24

77 mg (9.6 mmol) of lithium hydride was added to a dioxane solution of 2.0 g (6.0 mmol) of an intermediate B (Compound 2150) and the mixture was refluxed for 10 minutes. Then 1.5 g (10.0 mmol) of (+)-secondary butyl methanesulfonate {[α]¹⁸ _(D)=+1.49 (c=7, CHCl₃)} was added and the mixture was further refluxed for one hour. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 1.1 g (2.8 mmol) of the present compound (Compound (−)-502).

[α]¹⁸ _(D)=−0.98 (c=8.5, CHCl₃)

Production Example 25

70 mg (8.8 mmol) of lithium hydride was added to a dioxane solution of 1.9 g (5.8 mmol) of an intermediate B (Compound 2150) and the mixture was refluxed for 10 minutes. Then 1.4 g (9.2 mmol) of (−)-secondary butyl methanesulfonate {[α]¹⁸ _(D)=−1.43 (c=7, CHCl₃) was added and the mixture was further refluxed for one hour. 1,4-dioxane was distilled off under reduced pressure and water was added to the residue. The solution was extracted with ethyl acetate and the organic layer was washed with water. The solvent was distilled off under reduced pressure and the residue was washed with an ethyl acetate/hexane mixed solvent to obtain 1.1 g (2.8 mmol) of the present compound (Compound (+)-502).

[α]¹⁸ _(D)=+0.90 (c=8.3, CHCl₃)

Example 26

0.50 g (1.52 mmol) of an intermediate B (Compound 2072) was added to a mixture of 0.0242 g (3.04 mmol) of lithium hydride and 10.00 g of dioxane and the mixture was stirred at the same temperature for 30 minutes. Then 0.42 g (3.04 mmol) of isopropyl mesylate was slowly added dropwise, and after the completion of this dropwise addition, the mixture was heated to 100° C. and reacted at the same temperature for 2 hours. After cooling, 10.00 g of a 5% hydrochloric acid solution was added and the mixture was extracted twice with 20.00 g of toluene. The organic layers were joined and dried over magnesium sulfate, and then the solvent was distilled away. The residue was crystallized by adding n-hexane, then filtered, washed with n-hexane and dried to give 0.59 g (LC area metric percentage value: 77.4%) of the present compound (Compound No. 203).

Example 27

0.50 g (1.52 mmol) of an intermediate B (Compound 2072) was added to a mixture of 0.128 g (3.04 mmol) of lithium hydroxide monohydrate and 20.00 g of toluene at room temperature, and the mixture was subjected to azeotropic dehydration by heating under reflux for 2 hours. After cooling, toluene was perfectly distilled away and the residue was dried. To the resulting solid, 10.00 g of dioxane was added, followed by slow dropwise addition of 0.42 g (3.04 mmol) of isopropyl mesylate at room temperature. After the completion of this dropwise addition, the mixture was heated to 100° C. and stirred at the same temperature for 2 hours. Thereafter, the mixture was cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The organic layers were combined and dried over magnesium sulfate, and then the solvent was distilled off. The residue was crystallized by adding n-hexane, then filtered, washed with n-hexane and dried to obtain 0.45 g (LC area metric percentage value: 64.6%) of the present compound (Compound 203).

Example 28

0.50 g (1.51 mmol) of an intermediate B (Compound 2150) was added to a mixture of 0.0239 g (3.02 mmol) of lithium hydride and 10.00 g of dioxane at room temperature and stirred at the same temperature for 30 minutes. Then 0.42 g (3.02 mmol) of isopropyl mesylate was slowly added dropwise, after which the mixture was heated to 100° C. and stirred at the same temperature for 2 hours. Then the mixture was cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The organic layers were combined and dried over magnesium sulfate. The solvent was distilled off and the residue was subjected to silica gel column chromatography to obtain 0.42 g (LC areametric percentage value: 95.9%) of the present compound (Compound 411).

Example 29

0.50 g (1.80 mmol) of an intermediate B (Compound 2147) was added to a mixture of 0.0287 g (3.60 mmol) of lithium hydride and 10.00 g of dioxane, and the mixture was stirred at the same temperature for 30 minutes. Then 0.55 g (3.60 mmol) of sec-butyl mesylate was slowly added dropwise, which was followed by heating to 100° C. and stirring at the same temperature for 2 hours. The mixture was then cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The organic layers were combined and dried over magnesium sulfate, after which the solvent was distilled off and the residue was subjected to silica gel column chromatography to obtain 0.42 g (LC areametric percentage value: 99.2%) of the present compound (Compound 499).

Example 30

0.50 g (1.80 mmol) of an intermediate B (Compound 2147) was added to a mixture of 0.0871 g (2.07 mmol) of lithium hydroxide monohydrate and 20.00 g of toluene at a room temperature and the mixture was subjected to azeotropic dehydration by heating under reflux for 2 hours. After cooling, toluene was perfectly distilled off and the residue was dried. To the resulting solid, 2.50 g of dioxane was added and then 0.38 g (2.43 mmol) of sec-butyl mesylate was slowly added dropwise at room temperature, after which the mixture was heated to 100° C. and stirred at the same temperature for 3 hours. The solution was cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The organic layers were combined and dried over magnesium sulfate, and the solvent was distilled off. The residue was crystallized by adding n-hexane, then filtered, washed with n-hexane and dried to obtain 0.44 g (LC areametric percentage value: 93.5%) of the present compound (Compound 499).

Example 31

A mixture of 0.0871 g (2.07 mmol) of lithium hydroxide monohydrate, 0.50 g (1.80 mmol) of an intermediate B (Compound 2147) and 2.50 g of dioxane was heated to 100° C. Then 0.37 g (2.43 mmol) of sec-butyl mesylate was slowly added dropwise at the same temperature, after which the mixture was stirred at the same temperature for 4 hours. The solution was cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The organic layers were combined and dried over magnesium sulfate, and the solvent was distilled off. The residue was crystallized by adding n-hexane, then filtered, washed with n-hexane and dried to obtain 0.42 g (LC areametric percentage value: 98.4%) of the present compound (Compound 499).

Example 32

A mixture of 0.0871 g (2.07 mmol) of lithium hydroxide monohydrate, 0.50 g (1.80 mmol) of an intermediate B (Compound 2147), 0.50 g of molecular sieves 3A and 2.50 g of dioxane was heated to 100° C., to which 0.37 g (2.43 mmol) of sec-butyl mesylate was slowly added dropwise at the same temperature. After the completion of dropwise addition, the mixture was stirred at the same temperature for 4 hours, then cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The organic layers were combined and dried over magnesium sulfate, and then the solvent was distilled off. The residue was crystallized by adding n-hexane, then filtered, washed with n-hexane and dried to obtain 0.45 g (LC areametric percentage value: 99.1%) of the present compound (Compound 499).

Example 33

A mixture of 1.00 g (3.60 mmol) of an intermediate B (Compound 2147), 0.50 g of molecular sieves 3A, 0.74 g (4.86 mmol) of sec-butyl mesylate and 5.00 g of dioxane was heated to 90° C., to which 0.174 g (4.14 mmol) of lithium hydroxide monohydrate was added in three portions over a period of 2 hours. Thereafter, the mixture was stirred at the same temperature for 5 hours, then cooled and, after adding 20.00 g of a 5% hydrochloric acid solution, extracted twice with 40.00 g of toluene. The organic layers were combined and dried over magnesium sulfate, and the solvent was distilled off. The residue was crystallized by adding n-hexane, then filtered, washed with n-hexane and dried to obtain 0.95 g (LC areameetric percentage value: 97.8%) of the present compound (Compound 499).

Example 34

0.50 g (1.90 mmol) of an intermediate B (Compound 2017) was added to a mixture of 0.0305 g (3.80 mmol) of lithium hydride and 10.00 g of dioxane at room temperature, and the mixture was stirred at the same temperature for 30 minutes. Then 0.58 g (3.80 mmol) of sec-butyl mesylate was slowly added dropwise, followed by heating to 100° C. and stirring at the same temperature for 4 hours. The solution was cooled and, after adding 10.00 g of a 5% hydrochloric acid solution, extracted twice with 20.00 g of toluene. The formed organic layers were combined and dried over magnesium sulfate, and the solvent was distilled off. The residue was crystallized by adding n-hexane, filtered, washed with n-hexane and dried to give 0.25 g (LC areametric percentage value: 95.2%) of the present compound (Compound 278) of m.p. 70.0° C.

Production Example 35

300 ml of 3N hydrochloric acid and 100 ml of ethanol were added to 107 g (313 mmol) of 3-amino-2-tert-butyl-1-isopropyl-4-(2,6-dichlorophenyl)-3-pyrazoline-5-one and stirred under the refluxing condition for 4 hours. Then ethanol was distilled off under reduced pressure and the aqueous layer was neutralized with a dilute sodium oxide solution. The precipitated solid was filtered out, washed with water and ethyl acetate, and dried in vacuo to obtain 88.4 g (309 mmol) of an intermediate A (Compound 1007).

¹H-NMR (CD₃OD, TMS) δ (ppm): 7.47 (1H), 7.33-7.36 (2H), 4.93 (2H), 4.41 (1H), 1.30 (6H).

Production Example 36

300 ml of 3N hydrochloric acid and 100 ml of ethanol were added to 54.6 g (181 mmol) of 3-amino-2-tert-butyl-1-sec-butyl-4-(2-methylphenyl)-3-pyrazoline-5-one and stirred under the refluxing condition for 4 hours. Then ethanol was distilled off under reduced pressure and the aqueous layer was neutralized with a sodium bicarbonate solution, and the precipitated solid was filtered out, washed with water and ethyl acetate, and dried in vacuo to obtain 35.3 g (144 mmol) of an intermediate A (Compound 1017).

¹H-NMR (CD₃OD, TMS) δ (ppm): 7.17 (4H), 4.83 (2H), 4.1 (1H), 2.25 (3H), 1.5-1.9 (2H), 1.21 (3H), 0.94 (3H).

Production Example 37

5.19 g (27.5 mmol) of 3-amino-4-(2-methylphenyl)-3-pyrazoline-5-one and 11.1 g (110 mmol) of triethylamine were suspended in tetrahydrofuran, to which 2.5 g (30.7 mmol) of chlorotrimethylsilane was added dropwise under cooling with ice-water. Then 3.7 g (30.7 mmol) of allyl chloroformate was added dropwise under cooling with ice-water. The mixture was stirred at room temperature for one hour and the formed precipitate was filtered out. 8 ml of water and 8 ml (140 mmol) of acetic acid were added to the filtrate and refluxed for 30 minutes. The reaction solution was cooled to room temperature and, after adding water, extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography to obtain 1.4 g (5.1 mmol) of an intermediate B (compound 2069). M.p. 187.4° C.

Example 38

59.02 g (0.148 mol) of a 10% sodium hydroxide solution was slowly added dropwise to a mixture of 30.00 g (0.123 mol) of 3-amino-4-(2,6-dichlorophenyl)-3-pyrazoline-5-one, 15.56 g (0.129 mol) of allyl chloroformate and 150.00 g of toluene at 25° C., after which the mixture was stirred at the same temperature for 2 hours. Then the mixture was made acid by adding a 5% hydrochloric acid solution and the precipitated crystals were filtered out, washed with 30.00 g of toluene and dried to obtain 36.84 g (LC areametric percentage value: 99.1%) of an intermediate B (Compound 2072) of m.p. 169.0° C.

Example 39

39.34 g (98.36 mmol) of a 10% sodium hydroxide solution was slowly added dropwise to a mixture of 20.00 g (81.97 mmol) of 3-amino-4-(2,6-dichlorophenyl)-3-pyrazoline-5-one, 10.72 g (86.07 mmol) of S-ethyl chlorothioformate and 100.00 g of toluene at 25° C. After the completion of dropwise addition, the mixture was stirred at the same temperature for 2 hours. Then the reaction mixture was made acid by adding a 5% hydrochloric acid solution and extracted with toluene and methyl tert-butyl ether. The organic layer was concentrated and the residue was subjected to silica gel column chromatography to obtain 19.16 g (LC areametric percentage value: 98.4%) of an intermediate B (Compound 2150) of m.p. 198.5° C.

Example 40

1.27 g (3.18 mmol) of a 10% sodium hydroxide solution was slowly added dropwise to a mixture of 0.50 g (2.65 mmol) of 3-amino-4-(2-methylphenyl)-3-pyrazoline-5-one, 0.33 g (2.78 mmol) of allyl chloroformate and 2.50 g of toluene at 25° C., after which the mixture was stirred at the same temperature for one hour. Then the reaction mixture was made acid by adding a 5% hydrochloric acid solution and extracted with toluene and methyl tert-butyl ether. The solvent was concentrated and the residue was subjected to silica gel column chromatography to obtain 0.56 g (LC areametric percentage value: 99.6%) of an intermediate B (Compound 2069).

Example 41

50.79 g (0.127 mol) of a 10% sodium hydroxide solution was slowly added dropwise to a mixture of 20.00 g (0.106 mol) of 3-amino-4-(2-methylphenyl)-3-pyrazoline-5-one, 13.84 g (0.111 mol) of S-ethyl chlorothioformate and 100.00 g of toluene at 25° C., after which the mixture was stirred at the same temperature for one hour. Then the reaction mixture was made acid by adding a 5% hydrochloric acid solution and extracted twice with 40.00 g of ethyl acetate. The organic layers were combined and dried over magnesium sulfate. The solvent was concentrated and the residue was subjected to silica gel column chromatography. After additional concentration, the residue was washed with 200 ml of a 1/9 ethyl acetate/n-hexane mixed solution and dried to obtain 24.39 g (LC areametric percentage value: 98.5%) of an intermediate B (Compound 2147) of m.p. 172.5° C.

Example 42

5.08 g (12.7 mmol) of a 10% sodium hydroxide solution was slowly added dropwise to a mixture of 2.00 g (10.6 mmol) of 3-amino-4-(2-methylphenyl)-3-pyrazoline-5-one, 1.21 g (11.1 mmol) of ethyl chloroformate and 10.00 g of toluene at 25° C., after which the mixture was stirred at the same temperature for one hour. Then the reaction mixture was made acid by adding a 5% hydrochloric acid solution and extracted twice with 10.00 g of ethyl acetate. The organic layers were combined and dried over magnesium sulfate, the solvent was concentrated and the residue was subjected to silica gel column chromatography to obtain 2.10 g (LC areametric percentage value: 98.9%) of an intermediate B (Compound 2017) of m.p. 161.5° C.

Examples of the present compounds are shown with Compound No. in Tables 1 to 41.

The compounds represented by the formula:

TABLE 1 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 1 2-F iPr Me 2 2-Cl iPr Me 3 2-Br iPr Me 4 2,6-F₂ iPr Me 5 2,6-Cl₂ iPr Me 6 2-F, 6-Cl iPr Me 7 2,3,5-Cl₃ iPr Me 8 2-CF₃ iPr Me 9 2-CH₃ iPr Me 10 2-OCH₃ iPr Me 11 2,6-(CH₃)₂ iPr Me 12 2-Cl, 6-CH₃ iPr Me 13 2-F, 6-CH₃ iPr Me 14 2-F iPr Et 15 2-Cl iPr Et 16 2-Br iPr Et 17 2,6-F₂ iPr Et 18 2,6-Cl₂ iPr Et 19 2-F, 6-Cl iPr Et 20 2,3,5-Cl₃ iPr Et 21 2-CF₃ iPr Et 22 2-CH₃ iPr Et 23 2-OCH₃ iPr Et 24 2,6-(CH₃)₂ iPr Et 25 2-Cl, 6-CH₃ iPr Et

TABLE 2 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 26 2-F, 6-CH₃ iPr Et 27 2-F iPr nPr 28 2-Cl iPr nPr 29 2-Br iPr nPr 30 2,6-F₂ iPr nPr 31 2,6-Cl₂ iPr nPr 32 2-F, 6-Cl iPr nPr 33 2,3,5-Cl₃ iPr nPr 34 2-CF₃ iPr nPr 35 2-CH₃ iPr nPr 36 2-OCH₃ iPr nPr 37 2,6-(CH₃)₂ iPr nPr 38 2-Cl, 6-CH₃ iPr nPr 39 2-F, 6-CH₃ iPr nPr 40 2-F iPr nBu 41 2-Cl iPr nBu 42 2-Br iPr nBu 43 2,6-F₂ iPr nBu 44 2,6-Cl₂ iPr nBu 45 2-F, 6-Cl iPr nBu 46 2,3,5-Cl₃ iPr nBu 47 2-CF₃ iPr nBu 48 2-CH₃ iPr nBu 49 2-OCH₃ iPr nBu 50 2,6-(CH₃)₂ iPr nBu

TABLE 3 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 51 2-Cl, 6-CH₃ iPr nBu 52 2-F, 6-CH₃ iPr nBu 53 2-F iPr nPen 54 2-Cl iPr nPen 55 2-Br iPr nPen 56 2,6-F₂ iPr nPen 57 2,6-Cl₂ iPr nPen 58 2-F, 6-Cl iPr nPen 59 2,3,5-Cl₃ iPr nPen 60 2-CF₃ iPr nPen 61 2-CH₃ iPr nPen 62 2-OCH₃ iPr nPen 63 2,6-(CH₃)₂ iPr nPen 64 2-Cl, 6-CH₃ iPr nPen 65 2-F, 6-CH₃ iPr nPen 66 2-F sBu Me 67 2-Cl sBu Me 68 2-Br sBu Me 69 2,6-F₂ sBu Me 70 2,6-Cl₂ sBu Me 71 2-F, 6-Cl sBu Me 72 2,3,5-Cl₃ sBu Me 73 2-CF₃ sBu Me 74 2-CH₃ sBu Me 75 2-OCH₃ sBu Me

TABLE 4 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 76 2,6-(CH₃)₂ sBu Me 77 2-Cl, 6-CH₃ sBu Me 78 2-F, 6-CH₃ sBu Me 79 2-F sBu Et 80 2-Cl sBu Et 81 2-Br sBu Et 82 2,6-F₂ sBu Et 83 2,6-Cl₂ sBu Et 84 2-F, 6-Cl sBu Et 85 2,3,5-Cl₃ sBu Et 86 2-CF₃ sBu Et 87 2-CH₃ sBu Et 88 2-OCH₃ sBu Et 89 2,6-(CH₃)₂ sBu Et 90 2-Cl, 6-CH₃ sBu Et 91 2-F, 6-CH₃ sBu Et 92 2-F sBu nPr 93 2-Cl sBu nPr 94 2-Br sBu nPr 95 2-CF₃ sBu nPr 96 2-CH₃ sBu nPr 97 2-OCH₃ sBu nPr 98 2,6-F₂ sBu nPr 99 2,6-Cl₂ sBu nPr 100 2,6-(CH₃)₂ sBu nPr

TABLE 5 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 101 2-F, 6-Cl sBu nPr 102 2,3,5-Cl₃ sBu nPr 103 2-Cl, 6-CH₃ sBu nPr 104 2-F, 6-CH₃ sBu nPr 105 2-F sBu nBu 106 2-Cl sBu nBu 207 2-Br sBu nBu 108 2-CF₃ sBu nBu 109 2-CH₃ sBu nBu 110 2-OCH₃ sBu nBu 111 2,6-F₂ sBu nBu 112 2,6-Cl₂ sBu nBu 113 2,6-(CH₃)₂ sBu nBu 114 2-F, 6-Cl sBu nBu 115 2,3,5-Cl₃ sBu nBu 116 2-Cl, 6-CH₃ sBu nBu 117 2-F, 6-CH₃ sBu nBu 118 2-F sBu nPen 119 2-Cl sBu nPen 120 2-Br sBu nPen 121 2-CF₃ sBu nPen 122 2-CH₃ sBu nPen 123 2-OCH₃ sBu nPen 124 2,6-F₂ sBu nPen 125 2,6-Cl₂ sBu nPen

TABLE 6 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 126 2,6-(CH₃)₂ sBu nPen 127 2-F, 6-Cl sBu nPen 128 2,3,5-Cl₃ sBu nPen 129 2-Cl, 6-CH₃ sBu nPen 130 2-F, 6-CH₃ sBu nPen 131 2-F iPr O-Me 132 2-Cl iPr O-Me 133 2-Br iPr O-Me 134 2-CF₃ iPr O-Me 135 2-CH₃ iPr O-Me 136 2-OCH₃ iPr O-Me 137 2,6-F₂ iPr O-Me 138 2,6-Cl₂ iPr O-Me 139 2,6-(CH₃)₂ iPr O-Me 140 2-F, 6-Cl iPr O-Me 141 2,3,5-Cl₃ iPr O-Me 142 2-Cl, 6-CH₃ iPr O-Ne 143 2-F, 6-CH₃ iPr O-Me 144 2-F iPr O-Et 145 2-Cl iPr O-Et 146 2-Br iPr O-Et 147 2-CF₃ iPr O-Et 148 2-CH₃ iPr O-Et 149 2-OCH₃ iPr O-Et 150 2,6-F₂ iPr O-Et

TABLE 7 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 151 2,6-Cl₂ iPr O-Et 152 2,6-(CH₃)₂ iPr O-Et 153 2-F, 6-Cl iPr O-Et 154 2,3,5-Cl₃ iPr O-Et 155 2-Cl, 6-CH₃ iPr O-Et 156 2-F, 6-CH₃ iPr O-Et 157 2-F iPr O-nPr 158 2-Cl iPr O-nPr 159 2-Br iPr O-nPr 160 2-CF₃ iPr O-nPr 161 2-CH₃ iPr O-nPr 162 2-OCH₃ iPr O-nPr 163 2,6-F₂ iPr O-nPr 164 2,6-Cl₂ iPr O-nPr 165 2,6-(CH₃)₂ iPr O-nPr 166 2-F, 6-Cl iPr O-nPr 167 2,3,5-Cl₃ iPr O-nPr 168 2-Cl, 6-CH₃ iPr O-nPr 169 2-F, 6-CH₃ iPr O-nPr 170 2-F iPr O-nBu 171 2-Cl iPr O-nBu 172 2-Br iPr O-nBu 173 2-CF₃ iPr O-nBu 174 2-CH₃ iPr O-nBu 175 2-OCH₃ iPr O-nBu

TABLE 8 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 176 2,6-F₂ iPr O-nBu 177 2,6-Cl₂ iPr O-nBu 178 2,6-(CH₃)₂ iPr O-nBu 179 2-F, 6-Cl iPr O-nBu 180 2,3,5-Cl₃ iPr O-nBu 181 2-Cl, 6-CH₃ iPr O-nBu 182 2-F, 6-CH₃ iPr O-nBu 183 2-F iPr O-iBu 184 2-Cl iPr O-iBu 185 2-Br iPr O-iBu 186 2-CF₃ iPr O-iBu 187 2-CH₃ iPr O-iBu 188 2-OCH₃ iPr O-iBu 189 2,6-F₂ iPr O-iBu 190 2,6-Cl₂ iPr O-iBu 191 2,6-(CH₃)₂ iPr O-iBu 192 2-F, 6-Cl iPr O-iBu 193 2,3,5-Cl₃ iPr O-iBu 194 2-Cl, 6-CH₃ iPr O-iBu 195 2-F, 6-CH₃ iPr O-iBu 196 2-F iPr O-Allyl 197 2-Cl iPr O-Allyl 198 2-Br iPr O-Allyl 199 2-CF₃ iPr O-Allyl 200 2-CH₃ iPr O-Allyl

TABLE 9 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 201 2-OCH₃ iPr O-Allyl 202 2,6-F iPr O-Allyl 203 2,6-Cl₂ iPr O-Allyl 204 2,6-(CH₃)₂ iPr O-Allyl 205 2-F, 6-Cl iPr O-Allyl 206 2,3,5-Cl₃ iPr O-Allyl 207 2-Cl, 6-CH₃ iPr O-Allyl 208 2-F, 6-CH₃ iPr O-Allyl 209 2-F iPr OCH₂-Allyl 210 2-Cl iPr OCH₂-Allyl 211 2-Br iPr OCH₂-Allyl 212 2-CF₃ iPr OCH₂-Allyl 213 2-CH₃ iPr OCH₂-Allyl 214 2-OCH₃ iPr OCH₂-Allyl 215 2,6-F₂ iPr OCH₂-Allyl 216 2,6-Cl₂ iPr OCH₂-Allyl 217 2,6-(CH₃)₂ iPr OCH₂-Allyl 218 2-F, 6-Cl iPr OCH₂-Allyl 219 2,3,5-Cl₃ iPr OCH₂-Allyl 220 2-Cl, 6-CH₃ iPr OCH₂-Allyl 221 2-F, 6-CH₃ iPr OCH₂-Allyl 222 2-F iPr OCH₂C≡CH 223 2-Cl iPr OCH₂C≡CH 224 2-Br iPr OCH₂C≡CH 225 2-CF₃ iPr OCH₂C≡CH

TABLE 10 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 226 2-CH₃ iPr OCH₂C≡CH 227 2-OCH₃ iPr OCH₂C≡CH 228 2,6-F₂ iPr OCH₂C≡CH 229 2,6-Cl₂ iPr OCH₂C≡CH 230 2,6-(CH₃)₂ iPr OCH₂C≡CH 231 2-F, 6-Cl iPr OCH₂C≡CH 232 2,3,5-Cl₃ iPr OCH₂C≡CH 233 2-Cl, 6-CH₃ iPr OCH₂C≡CH 234 2-F, 6-CH₃ iPr OCH₂C≡CH 235 2-F iPr OCH₂CH₂C≡CH 236 2-Cl iPr OCH₂CH₂C≡CH 237 2-Br iPr OCH₂CH₂C≡CH 238 2-CF₃ iPr OCH₂CH₂C≡CH 239 2-CH₃ iPr OCH₂CH₂C≡CH 240 2-OCH₃ iPr OCH₂CH₂C≡CH 241 2,6-F₂ iPr OCH₂CH₂C≡CH 242 2,6-Cl₂ iPr OCH₂CH₂C≡CH 243 2,6-(CH₃)₂ iPr OCH₂CH₂C≡CH 244 2-F, 6-Cl iPr OCH₂CH₂C≡CH 245 2,3,5-Cl₃ iPr OCH₂CH₂C≡CH 246 2-Cl, 6-CH₃ iPr OCH₂CH₂C≡CH 247 2-F, 6-CH₃ iPr OCH₂CH₂C≡CH 248 2-F iPr OCH₂C≡CCH₃ 249 2-Cl iPr OCH₂C≡CCH₃ 250 2-Br iPr OCH₂C≡CCH₃

TABLE 11 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 251 2-CF₃ iPr OCH₂C≡CCH₃ 252 2-CH₃ iPr OCH₂C≡CCH₃ 253 2-OCH₃ iPr OCH₂C≡CCH₃ 254 2,6-F₂ iPr OCH₂C≡CCH₃ 255 2,6-Cl₂ iPr OCH₂C≡CCH₃ 256 2-F, 6-Cl iPr OCH₂C≡CCH₃ 257 2,3,5-Cl₃ iPr OCH₂C≡CCH₃ 258 2-Cl, 6-CH₃ iPr OCH₂C≡CCH₃ 259 2-F, 6-CH₃ iPr OCH₂C≡CCH₃ 260 2,6-(CH₃)₂ iPr OCH₂C≡CCH₃ 261 2-F sBu O-Me 262 2-Cl sBu O-Me 263 2-Br sBu O-Me 264 2-CF₃ sBu O-Me 265 2-CH₃ sBu O-Me 266 2-OCH₃ sBu O-Ne 267 2,6-F₂ sBu O-Me 268 2,6-Cl₂ sBu O-Me 269 2,6-(CH₃)₂ sBu O-Me 270 2-F, 6-Cl sBu O-Me 271 2,3,5-Cl₃ sBu O-Me 272 2-Cl, 6-CH₃ sBu O-Me 273 2-F, 6-CH₃ sBu O-Me 274 2-F sBu O-Et 275 2-Cl sBu O-Et

TABLE 12 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 276 2-Br sBu O-Et 277 2-CF₃ sBu O-Et 278 2-CH₃ sBu O-Et 279 2-OCH₃ sBu O-Et 280 2,6-F₂ sBu O-Et 281 2,6-Cl₂ sBu O-Et 282 2,6-(CH₃)₂ sBu O-Et 283 2-F, 6-Cl sBu O-Et 284 2,3,5-Cl₃ sBu O-Et 285 2-Cl, 6-CH₃ sBu O-Et 286 2-F, 6-CH₃ sBu O-Et 287 2-F sBu O-nPr 288 2-Cl sBu O-nPr 289 2-Br sBu O-nPr 290 2-CF₃ sBu O-nPr 291 2-CH₃ sBu O-nPr 292 2-OCH₃ sBu O-nPr 293 2,6-F₂ sBu O-nPr 294 2,6-Cl₂ sBu O-nPr 295 2,6-(CH₃)₂ sBu O-nPr 296 2-F, 6-Cl sBu O-nPr 297 2,3,5-Cl₃ sBu O-nPr 298 2-Cl, 6-CH₃ sBu O-nPr 299 2-F, 6-CH₃ sBu O-nPr 300 2-F sBu O-nBu

TABLE 13 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 301 2-Cl sBu O-nBu 302 2-Br sBu O-nBu 303 2-CF₃ sBu O-nBu 304 2-CH₃ sBu O-nBu 305 2-OCH₃ sBu O-nBu 306 2,6-F₂ sBu O-nBu 307 2,6-Cl₂ sBu O-nBu 308 2,6-(CH₃)₂ sBu O-nBu 309 2-F, 6-Cl sBu O-nBu 310 2,3,5-Cl₃ sBu O-nBu 311 2-Cl, 6-CH₃ sBu O-nBu 312 2-F, 6-CH₃ sBu O-nBu 313 2-F sBu O-iBu 314 2-Cl sBu O-iBu 315 2-Br sBu O-iBu 316 2-CF₃ sBu O-iBu 317 2-CH₃ sBu O-iBu 318 2-OCH₃ sBu O-iBu 319 2,6-F₂ sBu O-iBu 320 2,6-Cl₂ sBu O-iBu 321 2,6-(CH₃)₂ sBu O-iBu 322 2-F, 6-Cl sBu O-iBu 323 2,3,5-Cl₃ sBu O-iBu 324 2-Cl, 6-CH₃ sBu O-iBu 325 2-F, 6-CH₃ sBu O-iBu

TABLE 14 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 326 2-F sBu O-Allyl 327 2-Cl sBu O-Allyl 328 2-Br sBu O-Allyl 329 2-CF₃ sBu O-Allyl 330 2-CH₃ sBu O-Allyl 331 2-OCH₃ sBu O-Allyl 332 2,6-F₂ sBu O-Allyl 333 2,6-Cl₂ sBu O-Allyl 334 2,6-(CH₃)₂ sBu O-Allyl 335 2-F, 6-Cl sBu O-Allyl 336 2,3,5-Cl₃ sBu O-Allyl 337 2-Cl, 6-CH₃ sBu O-Allyl 338 2-F, 6-CH₃ sBu O-Allyl 339 2-F sBu OCH₂-Allyl 340 2-Cl sBu OCH₂-Allyl 341 2-Br sBu OCH₂-Allyl 342 2-CF₃ sBu OCH₂-Allyl 343 2-CH₃ sBu OCH₂-Allyl 344 2-OCH₃ sBu OCH₂-Allyl 345 2,6-F₂ sBu OCH₂-Allyl 346 2,6-Cl₂ sBu OCH₂-Allyl 347 2,6-(CH₃)₂ sBu OCH₂-Allyl 348 2-F, 6-Cl sBu OCH₂-Allyl 349 2,3,5-Cl₃ sBu OCH₂-Allyl 350 2-Cl, 6-CH₃ sBu OCH₂-Allyl

TABLE 15 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 351 2-F, 6-CH₃ sBu OCH₂-Allyl 352 2-F sBu OCH₂C≡CH 353 2-Cl sBu OCH₂C≡CH 354 2-Br sBu OCH₂C≡CH 355 2-CF₃ sBu OCH₂C≡CH 356 2-CH₃ sBu OCH₂C≡CH 357 2-OCH₃ sBu OCH₂C≡CH 358 2,6-F₂ sBu OCH₂C≡CH 359 2,6-Cl₂ sBu OCH₂C≡CH 360 2,6-(CH₃)₂ sBu OCH₂C≡CH 361 2-F, 6-Cl sBu OCH₂C≡CH 362 2,3,5-Cl₃ sBu OCH₂C≡CH 363 2-Cl, 6-CH₃ sBu OCH₂C≡CH 364 2-F, 6-CH₃ sBu OCH₂C≡CH 365 2-F sBu OCH₂CH₂C≡CH 366 2-Cl sBu OCH₂CH₂C≡CH 367 2-Br sBu OCH₂CH₂C≡CH 368 2-CF₃ sBu OCH₂CH₂C≡CH 369 2-CH₃ sBu OCH₂CH₂C≡CH 370 2-OCH₃ sBu OCH₂CH₂C≡CH 371 2,6-F₂ sBu OCH₂CH₂C≡CH 372 2,6-Cl₂ sBu OCH₂CH₂C≡CH 373 2,6-(CH₃)₂ sBu OCH₂CH₂C≡CH 374 2-F, 6-Cl sBu OCH₂CH₂C≡CH 375 2,3,5-Cl₃ sBu OCH₂CH₂C≡CH

TABLE 16 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 376 2-Cl, 6-CH₃ sBu OCH₂CH₂C≡CH 377 2-F, 6-CH₃ sBu OCH₂CH₂C≡CH 378 2-F sBu OCH₂≡CCH₃ 379 2-Cl sBu OCH₂≡CCH₃ 380 2-Br sBu OCH₂≡CCH₃ 381 2-CF₃ sBu OCH₂≡CCH₃ 382 2-CH₃ sBu OCH₂≡CCH₃ 383 2-OCH₃ sBu OCH₂≡CCH₃ 384 2,6-F₂ sBu OCH₂≡CCH₃ 385 2,6-Cl₂ sBu OCH₂≡CCH₃ 386 2,6-(CH₃)₂ sBu OCH₂≡CCH₃ 387 2-F, 6-Cl sBu OCH₂≡CCH₃ 388 2,3,5-Cl₃ sBu OCH₂≡CCH₃ 389 2-Cl, 6-CH₃ sBu OCH₂≡CCH₃ 390 2-F, 6-CH₃ sBu OCH₂≡CCH₃ 391 2-F iPr S-Me 392 2-Cl iPr S-Me 393 2-Br iPr S-Me 394 2-CF₃ iPr S-Me 395 2-CH₃ iPr S-Me 396 2-OCH₃ iPr S-Me 397 2,6-F₂ iPr S-Me 398 2,6-Cl₂ iPr S-Me 399 2,6-(CH₃)₂ iPr S-Me 400 2-F, 6-Cl iPr S-Me

TABLE 17 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 401 2,3,5-Cl₃ iPr S-Me 402 2-Cl, 6-CH₃ iPr S-Me 403 2-F, 6-CH₃ iPr S-Me 404 2-F iPr S-Et 405 2-Cl iPr S-Et 406 2-Br iPr S-Et 407 2-CF₃ iPr S-Et 408 2-CH₃ iPr S-Et 409 2-OCH₃ iPr S-Et 410 2,6-F₂ iPr S-Et 411 2,6-Cl₂ iPr S-Et 412 2,6-(CH₃)₂ iPr S-Et 413 2-F, 6-Cl iPr S-Et 414 2,3,5-Cl₃ iPr S-Et 415 2-Cl, 6-CH₃ iPr S-Et 416 2-F, 6-CH₃ iPr S-Et 417 2-F iPr S-nPr 418 2-Cl iPr S-nPr 419 2-Br iPr S-nPr 420 2-CF₃ iPr S-nPr 421 2-CH₃ iPr S-nPr 422 2-OCH₃ iPr S-nPr 423 2,6-F₂ iPr S-nPr 424 2,6-Cl₂ iPr S-nPr 425 2,6-(CH₃)₂ iPr S-nPr

TABLE 18 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 426 2-F, 6-Cl iPr S-nPr 427 2,3,5-Cl₃ iPr S-nPr 428 2-Cl, 6-CH₃ iPr S-nPr 429 2-F, 6-CH₃ iPr S-nPr 430 2-F iPr S-nBu 431 2-Cl iPr S-nBu 432 2-Br iPr S-nBu 433 2-CF₃ iPr S-nBu 434 2-CH₃ iPr S-nBu 435 2-OCH₃ iPr S-nBu 436 2,6-F₂ iPr S-nBu 437 2,6-Cl₂ iPr S-nBu 438 2,6-(CH₃)₂ iPr S-nBu 439 2-F, 6-Cl iPr S-nBu 440 2,3,5-Cl₃ iPr S-nBu 441 2-Cl, 6-CH₃ iPr S-nBu 442 2-F, 6-CH₃ iPr S-nBu 443 2-F iPr S-iBu 444 2-Cl iPr S-iBu 445 2-Br iPr S-iBu 446 2-CF₃ iPr S-iBu 447 2-CH₃ iPr S-iBu 448 2-OCH₃ iPr S-iBu 449 2,6-F₂ iPr S-iBu 450 2,6-Cl₂ iPr S-iBu

TABLE 19 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 451 2,6-(CH₃)₂ iPr S-iBu 452 2-F, 6-Cl iPr S-iBu 453 2,3,5-Cl₃ iPr S-iBu 454 2-Cl, 6-CH₃ iPr S-iBu 455 2-F, 6-CH₃ iPr S-iBu 456 2-F iPr S-Allyl 457 2-Cl iPr S-Allyl 458 2-Br iPr S-Allyl 459 2-CF₃ iPr S-Allyl 460 2-CH₃ iPr S-Allyl 461 2-OCH₃ iPr S-Allyl 462 2,6-F₂ iPr S-Allyl 463 2,6-Cl₂ iPr S-Allyl 464 2,6-(CH₃)₂ iPr S-Allyl 465 2-F, 6-Cl iPr S-Allyl 466 2,3,5-Cl₃ iPr S-Allyl 467 2-Cl, 6-CH₃ iPr S-Allyl 468 2-F, 6-CH₃ iPr S-Allyl 469 2-F iPr SCH₂-Allyl 470 2-Cl iPr SCH₂-Allyl 471 2-Br iPr SCH₂-Allyl 472 2-CF₃ iPr SCH₂-Allyl 473 2-CH₃ iPr SCH₂-Allyl 474 2-OCH₃ iPr SCH₂-Allyl 475 2,6-F₂ iPr SCH₂-Allyl

TABLE 20 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 476 2,6-Cl₂ iPr SCH₂-Allyl 477 2,6-(CH₃)₂ iPr SCH₂-Allyl 478 2-F, 6-Cl iPr SCH₂-Allyl 479 2,3,5-Cl₃ iPr SCH₂-Allyl 480 2-Cl, 6-CH₃ iPr SCH₂-Allyl 481 2-F, 6-CH₃ iPr SCH₂-Allyl 482 2-F sBu S-Me 483 2-Cl sBu S-Me 484 2-Br sBu S-Me 485 2-CF₃ sBu S-Me 486 2-CH₃ sBu S-Me 487 2-OCH₃ sBu S-Me 488 2,6-F₂ sBu S-Me 489 2,6-Cl₂ sBu S-Me 490 2,6-(CH₃)₂ sBu S-Me 491 2-F, 6-Cl sBu S-Me 492 2,3,5-Cl₃ sBu S-Me 493 2-Cl, 6-CH₃ sBu S-Me 494 2-F, 6-CH₃ sBu S-Me 495 2-F sBu S-Et 496 2-Cl sBu S-Et 497 2-Br sBu S-Et 498 2-CF₃ sBu S-Et 499 2-CH₃ sBu S-Et 500 2-OCH₃ sBu S-Et

TABLE 21 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 501 2,6-F₂ sBu S-Et 502 2,6-Cl₂ sBu S-Et 503 2,6-(CH₃)₂ sBu S-Et 504 2-F, 6-Cl sBu S-Et 505 2,3,5-Cl₃ sBu S-Et 506 2-Cl, 6-CH₃ sBu S-Et 507 2-F, 6-CH₃ sBu S-Et 508 2-F sBu S-nPr 509 2-Cl sBu S-nPr 510 2-Br sBu S-nPr 511 2-CF₃ sBu S-nPr 512 2-CH₃ sBu S-nPr 513 2-OCH₃ sBu S-nPr 514 2,6-F₂ sBu S-nPr 515 2,6-Cl₂ sBu S-nPr 516 2,6-(CH₃)₂ sBu S-nPr 517 2-F, 6-Cl sBu S-nPr 518 2,3,5-Cl₃ sBu S-nPr 519 2-Cl, 6-CH₃ sBu S-nPr 520 2-F, 6-CH₃ sBu S-nPr 521 2-F sBu S-nBu 522 2-Cl sBu S-nBu 523 2-Br sBu S-nBu 524 2-CF₃ sBu S-nBu 525 2-CH₃ sBu S-nBu

TABLE 22 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 526 2-OCH₃ sBu S-nBu 527 2,6-F₂ sBu S-nBu 528 2,6-Cl₂ sBu S-nBu 529 2,6-(CH₃)₂ sBu S-nBu 530 2-F, 6-Cl sBu S-nBu 531 2,3,5-Cl₃ sBu S-nBu 532 2-Cl, 6-CH₃ sBu S-nBu 533 2-F, 6-CH₃ sBu S-nBu 534 2-F sBu S-iBu 535 2-Cl sBu S-iBu 536 2-Br sBu S-iBu 537 2-CF₃ sBu S-iBu 538 2-CH₃ sBu S-iBu 539 2-OCH₃ sBu S-iBu 540 2,6-F₂ sBu S-iBu 541 2,6-Cl₂ sBu S-iBu 542 2,6-(CH₃)₂ sBu S-iBu 543 2-F, 6-Cl sBu S-iBu 544 2,3,5-Cl₃ sBu S-iBu 545 2-Cl, 6-CH₃ sBu S-iBu 546 2-F, 6-CH₃ sBu S-iBu 547 2-F sBu S-Allyl 548 2-Cl sBu S-Allyl 549 2-Br sBu S-Allyl 550 2-CF₃ sBu S-Allyl

TABLE 23 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 551 2-CH₃ sBu S-Allyl 552 2-OCH₃ sBu S-Allyl 553 2,6-F₂ sBu S-Allyl 554 2,6-Cl₂ sBu S-Allyl 555 2,6-(CH₃)₂ sBu S-Allyl 556 2-F, 6-Cl sBu S-Allyl 557 2,3,5-Cl₃ sBu S-Allyl 558 2-Cl, 6-CH₃ sBu S-Allyl 559 2-F, 6-CH₃ sBu S-Allyl 560 2-F sBu SCH₂-Allyl 561 2-Cl sBu SCH₂-Allyl 562 2-Br sBu SCH₂-Allyl 563 2-CF₃ sBu SCH₂-Allyl 564 2-CH₃ sBu SCH₂-Allyl 565 2-OCH₃ sBu SCH₂-Allyl 566 2,6-F₂ sBu SCH₂-Allyl 567 2,6-Cl₂ sBu SCH₂-Allyl 568 2,6-(CH₃)₂ sBu SCH₂-Allyl 569 2-F, 6-Cl sBu SCH₂-Allyl 570 2,3,5-Cl₃ sBu SCH₂-Allyl 571 2-Cl, 6-CH₃ sBu SCH₂-Allyl 572 2-F, 6-CH₃ sBu SCH₂-Allyl 573 2-Me iPr cPr 574 2,6-Cl₂ iPr cPr 575 2-Me sBu cPr

TABLE 24 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 576 2,6-Cl₂ sBu cPr 577 2-Me iPr OCH₂-cPr 578 2,6-Cl₂ iPr OCH₂-cPr 579 2-Me sBu OCH₂-cPr 580 2,6-Cl₂ sBu OCH₂-cPr 581 2-Me iPr OCH₂CH₂Cl 582 2,6-Cl₂ iPr OCH₂CH₂Cl 583 2-Me sBu OCH₂CH₂Cl 584 2,6-Cl₂ sBu OCH₂CH₂Cl 585 2-Me iPr OCH₂Ph 586 2,6-Cl₂ iPr OCH₂Ph 587 2-Me sBu OCH₂Ph 588 2,6-Cl₂ sBu OCH₂Ph 589 2-Me iPr OCH₂C(Me)=CH₂ 590 2,6-Cl₂ iPr OCH₂C(Me)=CH₂ 591 2-Me sBu OCH₂C(Me)=CH₂ 592 2,6-Cl₂ sBu OCH₂C(Me)=CH₂ 593 2-Me Et O-Allyl 594 2-Me Et OCH₂C≡CH 595 2-Me Et SEt 596 2-Me Et S-Allyl 597 2,6-Cl₂ Et O-Allyl 598 2,6-Cl₂ Et OCH₂C≡CH 599 2,6-Cl₂ Et SEt 600 2,6-Cl₂ Et S-Allyl

TABLE 25 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X (−) −499 2-Me sBu SEt (+) −499 2-Me sBu SEt (−) −502 2,6-Cl₂ sBu SEt (+) −502 2,6-Cl₂ sBu SEt

The compounds represented by the formula:

TABLE 26 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 601 2-F iPr O-Me 602 2-Cl iPr O-Me 603 2-Br iPr O-Me 604 2-CF₃ iPr O-Me 605 2-CH₃ iPr O-Me 606 2-OCH₃ iPr O-Me 607 2,6-F₂ iPr O-Me 608 2,6-Cl₂ iPr O-Me 609 2,6-(CH₃)₂ iPr O-Me 610 2-F, 6-Cl iPr O-Me 611 2,3,5-Cl₃ iPr O-Me 612 2-Cl, 6-CH₃ iPr O-Me 613 2-F, 6-CH₃ iPr O-Me 614 2-F iPr O-Et 615 2-Cl iPr O-Et 616 2-Br iPr O-Et 617 2-CF₃ iPr O-Et 618 2-CH₃ iPr O-Et 619 2-OCH₃ iPr O-Et 620 2,6-F₂ iPr O-Et 621 2,6-Cl₂ iPr O-Et 622 2,6-(CH₃)₂ iPr O-Et 623 2-F, 6-Cl iPr O-Et 624 2,3,5-Cl₃ iPr O-Et 625 2-Cl, 6-CH₃ iPr O-Et

TABLE 27 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 626 2-F, 6-CH₃ iPr O-Et 627 2-F iPr O-nPr 628 2-Cl iPr O-nPr 629 2-Br iPr O-nPr 630 2-CF₃ iPr O-nPr 631 2-CH₃ iPr O-nPr 632 2-OCH₃ iPr O-nPr 633 2,6-F₂ iPr O-nPr 634 2,6-Cl₂ iPr O-nPr 635 2,6-(CH₃)₂ iPr O-nPr 636 2-F, 6-Cl iPr O-nPr 637 2,3,5-Cl₃ iPr O-nPr 638 2-Cl, 6-CH₃ iPr O-nPr 639 2-F, 6-CH₃ iPr O-nPr 640 2-F iPr O-nBu 641 2-Cl iPr O-nBu 642 2-Br iPr O-nBu 643 2-CF₃ iPr O-nBu 644 2-CH₃ iPr O-nBu 645 2-OCH₃ iPr O-nBu 646 2,6-F₂ iPr O-nBu 647 2,6-Cl₂ iPr O-nBu 648 2,6-(CH₃)₂ iPr O-nBu 649 2-F, 6-Cl iPr O-nBu 650 2,3,5-Cl₃ iPr O-nBu

TABLE 28 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 651 2-Cl, 6-CH₃ iPr O-nBu 652 2-F, 6-CH₃ iPr O-nBu 653 2-F iPr O-iBu 654 2-Cl iPr O-iBu 655 2-Br iPr O-iBu 656 2-CF₃ iPr O-iBu 657 2-CH₃ iPr O-iBu 658 2-OCH₃ iPr O-iBu 659 2,6-F₂ iPr O-iBu 660 2,6-Cl₂ iPr O-iBu 661 2,6-(CH₃)₂ iPr O-iBu 662 2-F, 6-Cl iPr O-iBu 663 2,3,5-Cl₃ iPr O-iBu 664 2-Cl, 6-CH₃ iPr O-iBu 665 2-F, 6-CH₃ iPr O-iBu 666 2-F iPr O-Allyl 667 2-Cl iPr O-Allyl 668 2-Br iPr O-Allyl 669 2-CF₃ iPr O-Allyl 670 2-CH₃ iPr O-Allyl 671 2-OCH₃ iPr O-Allyl 672 2,6-F₂ iPr O-Allyl 673 2,6-Cl₂ iPr O-Allyl 674 2,6-(CH₃)₂ iPr O-Allyl 675 2-F, 6-Cl iPr O-Allyl

TABLE 29 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 676 2,3,5-Cl₃ iPr O-Allyl 677 2-Cl, 6-CH₃ iPr O-Allyl 678 2-F, 6-CH₃ iPr O-Allyl 679 2-F iPr OCH₂-Allyl 680 2-Cl iPr OCH₂-Allyl 681 2-Br iPr OCH₂-Allyl 682 2-CF₃ iPr OCH₂-Allyl 683 2-CH₃ iPr OCH₂-Allyl 684 2-OCH₃ iPr OCH₂-Allyl 685 2,6-F₂ iPr OCH₂-Allyl 686 2,6-Cl₂ iPr OCH₂-Allyl 687 2,6-(CH₃)₂ iPr OCH₂-Allyl 688 2-F, 6-Cl iPr OCH₂-Allyl 689 2,3,5-Cl₃ iPr OCH₂-Allyl 690 2-Cl, 6-CH₃ iPr OCH₂-Allyl 691 2-F, 6-CH₃ iPr OCH₂-Allyl 692 2-F iPr OCH₂C≡CH 693 2-Cl iPr OCH₂C≡CH 694 2-Br iPr OCH₂C≡CH 695 2-CF₃ iPr OCH₂C≡CH 696 2-CH₃ iPr OCH₂C≡CH 697 2-OCH₃ iPr OCH₂C≡CH 698 2,6-F₂ iPr OCH₂C≡CH 699 2,6-Cl₂ iPr OCH₂C≡CH 700 2,6-(CH₃)₂ iPr OCH₂C≡CH

TABLE 30 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 701 2-F, 6-Cl iPr OCH₂C≡CH 702 2,3,5-Cl₃ iPr OCH₂C≡CH 703 2-Cl, 6-CH₃ iPr OCH₂C≡CH 704 2-F, 6-CH₃ iPr OCH₂C≡CH 705 2-F iPr OCH₂CH₂C≡CH 706 2-Cl iPr OCH₂CH₂C≡CH 707 2-Br iPr OCH₂CH₂C≡CH 708 2-CF₃ iPr OCH₂CH₂C≡CH 709 2-CH₃ iPr OCH₂CH₂C≡CH 710 2-OCH₃ iPr OCH₂CH₂C≡CH 711 2,6-F₂ iPr OCH₂CH₂C≡CH 712 2,6-Cl₂ iPr OCH₂CH₂C≡CH 713 2,6-(CH₃)₂ iPr OCH₂CH₂C≡CH 714 2-F, 6-Cl iPr OCH₂CH₂C≡CH 715 2,3,5-Cl₃ iPr OCH₂CH₂C≡CH 716 2-Cl, 6-CH₃ iPr OCH₂CH₂C≡CH 717 2-F, 6-CH₃ iPr OCH₂CH₂C≡CH 718 2-F iPr OCH₂C≡CCH₃ 719 2-Cl iPr OCH₂C≡CCH₃ 720 2-Br iPr OCH₂C≡CCH₃ 721 2-CF₃ iPr OCH₂C≡CCH₃ 722 2-CH₃ iPr OCH₂C≡CCH₃ 723 2-OCH₃ iPr OCH₂C≡CCH₃ 724 2,6-F₂ iPr OCH₂C≡CCH₃ 725 2,6-Cl₂ iPr OCH₂C≡CCH₃

TABLE 31 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 726 2,6-(CH₃)₂ iPr OCH₂C≡CCH₃ 727 2-F, 6-Cl iPr OCH₂C≡CCH₃ 728 2,3,5-Cl₃ iPr OCH₂C≡CCH₃ 729 2-Cl, 6-CH₃ iPr OCH₂C≡CCH₃ 730 2-F, 6-CH₃ iPr OCH₂C≡CCH₃ 731 2-F sBu O-Me 732 2-Cl sBu O-Me 733 2-Br sBu O-Me 734 2-CF₃ sBu O-Me 735 2-CH₃ sBu O-Me 736 2-OCH₃ sBu O-Me 737 2,6-F₂ sBu O-Me 738 2,6-Cl₂ sBu O-Me 739 2,6-(CH₃)₂ sBu O-Me 740 2-F, 6-Cl sBu O-Me 741 2,3,5-Cl₃ sBu O-Me 742 2-Cl, 6-CH₃ sBu O-Me 743 2-F, 6-CH₃ sBu O-Me 744 2-F sBu O-Et 745 2-Cl sBu O-Et 746 2-Br sBu O-Et 747 2-CF₃ sBu O-Et 748 2-CH₃ sBu O-Et 749 2-OCH₃ sBu O-Et 750 2,6-F₂ sBu O-Et

TABLE 32 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 751 2,6-Cl₂ sBu O-Et 752 2,6-(CH₃)₂ sBu O-Et 753 2-F, 6-Cl sBu O-Et 754 2,3,5-Cl₃ sBu O-Et 755 2-Cl, 6-CH₃ sBu O-Et 756 2-F, 6-CH₃ sBu O-Et 757 2-F sBu O-nPr 758 2-Cl sBu O-nPr 759 2-Br sBu O-nPr 760 2-CF₃ sBu O-nPr 761 2-CH₃ sBu O-nPr 762 2-OCH₃ sBu O-nPr 763 2,6-F₂ sBu O-nPr 764 2,6-Cl₂ sBu O-nPr 765 2,6-(CH₃)₂ sBu O-nPr 766 2-F, 6-Cl sBu O-nPr 767 2,3,5-Cl₃ sBu O-nPr 768 2-Cl, 6-CH₃ sBu O-nPr 769 2-F, 6-CH₃ sBu O-nPr 770 2-F sBu O-nBu 771 2-Cl sBu O-nBu 772 2-Br sBu O-nBu 773 2-CF₃ sBu O-nBu 774 2-CH₃ sBu O-nBu 775 2-OCH₃ sBu O-nBu

TABLE 33 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 776 2,6-F₂ sBu O-nBu 777 2,6-Cl₂ sBu O-nBu 778 2,6-(CH₃)₂ sBu O-nBu 779 2-F, 6-Cl sBu O-nBu 780 2,3,5-Cl₃ sBu O-nBu 781 2-Cl, 6-CH₃ sBu O-nBu 782 2-F, 6-CH₃ sBu O-nBu 783 2-F sBu O-iBu 784 2-Cl sBu O-iBu 785 2-Br sBu O-iBu 786 2-CF₃ sBu O-iBu 787 2-CH₃ sBu O-iBu 788 2-OCH₃ sBu O-iBu 789 2,6-F₂ sBu O-iBu 790 2,6-Cl₂ sBu O-iBu 791 2,6-(CH₃)₂ sBu O-iBu 792 2-F, 6-Cl sBu O-iBu 793 2,3,5-Cl₃ sBu O-iBu 794 2-Cl, 6-CH₃ sBu O-iBu 795 2-F, 6-CH₃ sBu O-iBu 796 2-F sBu O-Allyl 797 2-Cl sBu O-Allyl 798 2-Br sBu O-Allyl 799 2-CF₃ sBu O-Allyl 800 2-CH₃ sBu O-Allyl

TABLE 34 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 801 2-OCH₃ sBu O-Allyl 802 2,6-F₂ sBu O-Allyl 803 2,6-Cl₂ sBu O-Allyl 804 2,6-(CH₃)₂ sBu O-Allyl 805 2-F, 6-Cl sBu O-Allyl 806 2,3,5-Cl₃ sBu O-Allyl 807 2-Cl, 6-CH₃ sBu O-Allyl 808 2-F, 6-CH₃ sBu O-Allyl 809 2-F sBu OCH₂-Allyl 810 2-Cl sBu OCH₂-Allyl 811 2-Br sBu OCH₂-Allyl 812 2-CF₃ sBu OCH₂-Allyl 813 2-CH₃ sBu OCH₂-Allyl 814 2-OCH₃ sBu OCH₂-Allyl 815 2,6-F₂ sBu OCH₂-Allyl 816 2,6-Cl₂ sBu OCH₂-Allyl 817 2,6-(CH₃)₂ sBu OCH₂-Allyl 818 2-F, 6-Cl sBu OCH₂-Allyl 819 2,3,5-Cl₃ sBu OCH₂-Allyl 820 2-Cl, 6-CH₃ sBu OCH₂-Allyl 821 2-F, 6-CH₃ sBu OCH₂-Allyl 822 2-F sBu OCH₂C≡CH 823 2-Cl sBu OCH₂C≡CH 824 2-Br sBu OCH₂C≡CH 825 2-CF₃ sBu OCH₂C≡CH

TABLE 35 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 826 2-CH₃ sBu OCH₂C≡CH 827 2-OCH₃ sBu OCH₂C≡CH 828 2,6-F₂ sBu OCH₂C≡CH 829 2,6-Cl₂ sBu OCH₂C≡CH 830 2,6-(CH₃)₂ sBu OCH₂C≡CH 831 2-F, 6-Cl sBu OCH₂C≡CH 832 2,3,5-Cl₃ sBu OCH₂C≡CH 833 2-Cl, 6-CH₃ sBu OCH₂C≡CH 834 2-F, 6-CH₃ sBu OCH₂C≡CH 835 2-F sBu OCH₂CH₂C≡CH 836 2-Cl sBu OCH₂CH₂C≡CH 837 2-Br sBu OCH₂CH₂C≡CH 838 2-CF₃ sBu OCH₂CH₂C≡CH 839 2-CH₃ sBu OCH₂CH₂C≡CH 840 2-OCH₃ sBu OCH₂CH₂C≡CH 841 2,6-F₂ sBu OCH₂CH₂C≡CH 842 2,6-Cl₂ sBu OCH₂CH₂C≡CH 843 2,6-(CH₃)₂ sBu OCH₂CH₂C≡CH 844 2-F, 6-Cl sBu OCH₂CH₂C≡CH 845 2,3,5-Cl₃ sBu OCH₂CH₂C≡CH 846 2-Cl, 6-CH₃ sBu OCH₂CH₂C≡CCH 847 2-F, 6-CH₃ sBu OCH₂CH₂C≡CCH 848 2-F sBu OCH₂C≡CCH₃ 849 2-Cl sBu OCH₂C≡CCH₃ 850 2-Br sBu OCH₂C≡CCH₃

TABLE 36 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 851 2-CF₃ sBu OCH₂C≡CCH₃ 852 2-CH₃ sBu OCH₂C≡CCH₃ 853 2-OCH₃ sBu OCH₂C≡CCH₃ 854 2,6-F₂ sBu OCH₂C≡CCH₃ 855 2,6-Cl₂ sBu OCH₂C≡CCH₃ 856 2,6-(CH₃)₂ sBu OCH₂C≡CCH₃ 857 2-F, 6-Cl sBu OCH₂C≡CCH₃ 858 2,3,5-Cl₃ sBu OCH₂C≡CCH₃ 859 2-Cl, 6-CH₃ sBu OCH₂C≡CCH₃ 860 2-F, 6-CH₃ sBu OCH₂C≡CCH₃ 861 2,6-Cl₂ iPr OCH₂-cPr 862 2,6-Cl₂ sBu OCH₂-cPr 863 2-CH₃ iPr OCH₂-cPr 864 2-CH₃ sBu OCH₂-cPr

TABLE 37 Compound No. R¹, R², R³, R⁴, R⁵ R⁶ X 865 2,6-Cl₂ iPr OCH₂CH₂Cl 866 2,6-Cl₂ sBu OCH₂CH₂Cl 867 2-CH₃ iPr OCH₂CH₂Cl 868 2-CH₃ sBu OCH₂CH₂Cl 869 2,6-Cl₂ iPr OCH₂Ph 870 2,6-Cl₂ sBu OCH₂Ph 871 2-CH₃ iPr OCH₂Ph 872 2-CH₃ sBu OCH₂Ph 873 2,6-Cl₂ iPr OCH₂C(Me)=CH₂ 874 2,6-Cl₂ sBu OCH₂C(Me)=CH₂ 875 2-CH₃ iPr OCH₂C(Me)=CH₂ 876 2-CH₃ sBu OCH₂C(Me)=CH₂

The compounds represented by the formula:

TABLE 38 Compound No. R⁶ X 877 iPr O-Me 878 iPr O-Et 879 iPr O-nPr 880 iPr O-nBu 881 iPr O-iBu 882 iPr O-Allyl 883 iPr OCH₂-Allyl 884 iPr OCH₂C≡CH 885 iPr OCH₂CH₂C≡CH 886 iPr OCH₂C≡CCH₃ 887 sBu O-Me 888 sBu O-Et 889 sBu O-nPr 890 sBu O-nBu 891 sBu O-iBu 892 sBu O-Allyl 893 sBu OCH₂-Allyl 894 sBu OCH₂C≡CH 895 sBu OCH₂CH₂C≡CH 896 sBu OCH₂C≡CCH₃ 897 iPr Me 898 iPr Et 899 iPr nPr 900 sBu Me 901 sBu Et

TABLE 39 Compound No. R⁶ X 902 sBu nPr 903 iPr S-Me 904 iPr S-Et 905 iPr S-nPr 906 iPr S-nBu 907 iPr S-Allyl 908 iPr SCH₂-Allyl 909 sBu S-Me 910 sBu S-Et 911 sBu S-nPr 912 sBu S-nBu 913 sBu S-Allyl 914 sBu SCH₂-Allyl

The compounds represented by the formula:

TABLE 40 Compound No. R⁶ X 915 iPr O-Me 916 iPr O-Et 917 iPr O-nPr 918 iPr O-nBu 919 iPr O-iBu 920 iPr O-Allyl 921 iPr OCH₂-Allyl 922 iPr OCH₂C≡CH 923 iPr OCH₂CH₂C≡CH 924 iPr OCH₂C≡CCH₃ 925 sBu O-Me 926 sBu O-Et 927 sBu O-nPr 928 sBu O-nBu 929 sBu O-iBu 930 sBu O-Allyl 931 sBu OCH₂-Allyl 932 sBu OCH₂C≡CH 933 sBu OCH₂CH₂C≡CH 934 sBu OCH₂C≡CCH₃

TABLE 41 Compound No. R⁶ X 935 iPr Me 936 iPr Et 937 iPr nPr 938 sBu Me 939 sBu Et 940 sBu nPr

Examples of the intermediates A are shown with compound No. in Tables 42 to 44.

TABLE 42 Compound No. R¹¹R²¹, R³¹, R⁴¹, R⁵¹ R⁶¹ 1000 2-F iPr 1001 2-Cl iPr 1002 2-Br iPr 1003 2-CF₃ iPr 1004 2-CH₃ iPr 1005 2-OCH₃ iPr 1006 2,6-F₂ iPr 1007 2,6-Cl₂ iPr 1008 2,6-(CH₃)₂ iPr 1009 2-F, 6-Cl iPr 1010 2,3,5-Cl₃ iPr 1011 2-Cl, 6-CH₃ iPr 1012 2-F, 6-CH₃ iPr 1013 2-F sBu 1014 2-Cl sBu 1015 2-Br sBu 1016 2-CF₃ sBu 1017 2-CH₃ sBu 1018 2-OCH₃ sBu 1019 2,6-F₂ sBu 1020 2,6-Cl₂ sBu 1021 2,6(CH₃)₂ sBu 1022 2-F, 6-Cl sBu

TABLE 43 Compound No. R¹¹R²¹, R³¹, R⁴¹, R⁵¹ R⁶¹ 1023 2,3,5-Cl₃ sBu 1024 2-Cl, 6-CH₃ sBu 1025 2-F, 6-CH₃ sBu

The compounds represented by the formula:

TABLE 44 Compound No. R⁶¹ 1026 iPr 1027 sBu

Examples of the intermediates B are shown with No. in Tables 45 to 64.

The compounds represented by the formula:

TABLE 45 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2000 2-F O O-Me 2001 2-Cl O O-Me 2002 2-Br O O-Me 2003 2-CF₃ O O-Me 2004 2-CH₃ O O-Me 2005 2-OCH₃ O O-Ne 2006 2,6-F₂ O O-Me 2007 2,6-Cl₂ O O-Me 2008 2,6-(CH₃)₂ O O-Me 2009 2-F, 6-Cl O O-Me 2010 2,3,5-Cl₃ O O-Me 2011 2-Cl, 6-CH₃ O O-Me 2012 2-F, 6-CH₃ O O-Me 2013 2-F O O-Et 2014 2-Cl O O-Et 2015 2-Br O O-Et 2016 2-CF₃ O O-Et 2017 2-CH₃ O O-Et 2018 2-OCH₃ O O-Et 2019 2,6-F₂ O O-Et 2020 2,6-Cl₂ O O-Et 2021 2,6-(CH₃)₂ O O-Et 2022 2-F, 6-Cl O O-Et 2023 2,3,5-Cl₃ O O-Et 2024 2-Cl, 6-CH₃ O O-Et

TABLE 46 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2025 2-F, 6-CH₃ O O-Et 2026 2-F O nPr 2027 2-Cl O nPr 2028 2-Br O nPr 2029 2-CF₃ O nPr 2030 2-CH₃ O nPr 2031 2-OCH₃ O nPr 2032 2,6-F₂ O nPr 2033 2,6-Cl₂ O nPr 2034 2,6-(CH₃)₂ O nPr 2035 2-F, 6-Cl O nPr 2036 2,3,5-Cl₃ O nPr 2037 2-Cl, 6-CH₃ O nPr 2038 2-F, 6-CH₃ O nPr 2039 2-F O O-nBu 2040 2-Cl O O-nBu 2041 2-Br O O-nBu 2042 2-CF₃ O O-nBu 2043 2-CH₃ O O-nBu 2044 2-OCH₃ O O-nBu 2045 2,6-F₂ O O-nBu 2046 2,6-Cl₂ O O-nBu 2047 2,6-(CH₃)₂ O O-nBu 2048 2-F, 6-Cl O O-nBu 2049 2,3,5-Cl₃ O O-nBu

TABLE 47 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2050 2-Cl, 6-CH₃ O O-nBu 2051 2-F, 6-CH₃ O O-nBu 2052 2-F O O-iBu 2053 2-Cl O O-iBu 2054 2-Br O O-iBu 2055 2-CF₃ O O-iBu 2056 2-CH₃ O O-iBu 2057 2-OCH₃ O O-iBu 2058 2,6-F₂ O O-iBu 2059 2,6-Cl₂ O O-iBu 2060 2,6-(CH₃)₂ O O-iBu 2061 2-F, 6-Cl O O-iBu 2062 2,3,5-Cl₃ O O-iBu 2063 2-Cl, 6-CH₃ O O-iBu 2064 2-F, 6-CH₃ O O-iBu 2065 2-F O O-Allyl 2066 2-Cl O O-Allyl 2067 2-Br O O-Allyl 2068 2-CF₃ O O-Allyl 2069 2-CH₃ O O-Allyl 2070 2-OCH₃ O O-Allyl 2071 2,6-F₂ O O-Allyl 2072 2,6-Cl₂ O O-Allyl 2073 2,6-(CH₃)₂ O O-Allyl 2074 2-F, 6-Cl O O-Allyl

TABLE 48 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2075 2,3,5-Cl₃ O O-Allyl 2076 2-Cl, 6-CH₃ O O-Allyl 2077 2-F, 6-CH₃ O O-Allyl 2078 2-F O OCH₂-Allyl 2079 2-Cl O OCH₂-Allyl 2080 2-Br O OCH₂-Allyl 2081 2-CF₃ O OCH₂-Allyl 2082 2-CH₃ O OCH₂-Allyl 2083 2-OCH₃ O OCH₂-Allyl 2084 2,6-F₂ O OCH₂-Allyl 2085 2,6-Cl₂ O OCH₂-Allyl 2086 2,6-(CH₃)₂ O OCH₂-Allyl 2087 2-F, 6-Cl O OCH₂-Allyl 2088 2,3,5-Cl₃ O OCH₂-Allyl 2089 2-Cl, 6-CH₃ O OCH₂-Allyl 2090 2-F, 6-CH₃ O OCH₂-Allyl 2091 2-F O OCH₂O≡CH 2092 2-Cl O OCH₂O≡CH 2093 2-Br O OCH₂O≡CH 2094 2-CF₃ O OCH₂O≡CH 2095 2-CH₃ O OCH₂C≡CH 2096 2-OCH₃ O OCH₂C≡CH 2097 2,6-F₂ O OCH₂C≡CH 2098 2,6-Cl₂ O OCH₂C≡CH 2099 2,6-(CH₃)₂ O OCH₂C≡CH

TABLE 49 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2100 2-F, 6-Cl O OCH₂C≡CH 2101 2,3,5-Cl₃ O OCH₂C≡CH 2102 2-Cl, 6-CH₃ O OCH₂C≡CH 2103 2-F, 6-CH₃ O OCH₂C≡CH 2104 2-F O OCH₂CH₂C≡CH 2105 2-Cl O OCH₂CH₂C≡CH 2106 2-Br O OCH₂CH₂C≡CH 2107 2-CF₃ O OCH₂CH₂C≡CH 2108 2-CH₃ O OCH₂CH₂C≡CH 2109 2-OCH₃ O OCH₂CH₂C≡CH 2110 2,6-F₂ O OCH₂CH₂C≡CH 2111 2,6-Cl₂ O OCH₂CH₂C≡CH 2112 2,6-(CH₃)₂ O OCH₂CH₂C≡CH 2113 2-F, 6-Cl O OCH₂CH₂C≡CH 2114 2,3,5-Cl₃ O OCH₂CH₂C≡CH 2115 2-Cl, 6-CH₃ O OCH₂CH₂C≡CH 2116 2-F, 6-CH₃ O OCH₂CH₂C≡CH 2117 2-F O OCH₂C≡CCH₃ 2118 2-Cl O OCH₂C≡CCH₃ 2119 2-Br O OCH₂C≡CCH₃ 2120 2-CF₃ O OCH₂C≡CCH₃ 2121 2-CH₃ O OCH₂C≡CCH₃ 2122 2-OCH₃ O OCH₂C≡CCH₃ 2123 2,6-F₂ O OCH₂C≡CCH₃ 2124 2,6-Cl₂ O OCH₂C≡CCH₃

TABLE 50 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2125 2,6-(CH₃)₂ O OCH₂C≡CCH₃ 2126 2-F, 6-Cl O OCH₂C≡CCH₃ 2127 2,3,5-Cl₃ O OCH₂C≡CCH₃ 2128 2-Cl, 6-CH₃ O OCH₂C≡CCH₃ 2129 2-F, 6-CH₃ O OCH₂C≡CCH₃ 2130 2-F O S-Me 2131 2-Cl O S-Me 2132 2-Br O S-Ne 2133 2-CF₃ O S-Ne 2134 2-CH₃ O S-Me 2135 2-OCH₃ O S-Ne 2136 2,6-F₂ O S-Me 2137 2,6-Cl₂ O S-Me 2138 2,6-(CH₃)₂ O S-Me 2139 2-F, 6-Cl O S-Me 2140 2,3,5-Cl₃ O S-Me 2141 2-Cl, 6-CH₃ O S-Me 2142 2-F, 6-CH₃ O S-Me 2143 2-F O S-Et 2144 2-Cl O S-Et 2145 2-Br O S-Et 2146 2-CF₃ O S-Et 2147 2-CH₃ O S-Et 2148 2-OCH₃ O S-Et 2149 2,6-F₂ O S-Et

TABLE 51 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2150 2,6-Cl₂ O S-Et 2151 2,6-(CH₃)₂ O S-Et 2152 2-F, 6-Cl O S-Et 2153 2,3,5-Cl₃ O S-Et 2154 2-Cl, 6-CH₃ O S-Et 2155 2-F, 6-CH₃ O S-Et 2156 2-F O S-nPr 2157 2-Cl O S-nPr 2158 2-Br O S-nPr 2159 2-CF₃ O S-nPr 2160 2-CH₃ O S-nPr 2161 2-OCH₃ O S-nPr 2162 2,6-F₂ O S-nPr 2163 2,6-Cl₂ O S-nPr 2164 2,6-(CH₃)₂ O S-nPr 2165 2-F, 6-Cl O S-nPr 2166 2,3,5-Cl₃ O S-nPr 2167 2-Cl, 6-CH₃ O S-nPr 2168 2-F, 6-CH₃ O S-nPr 2169 2-F O S-nBu 2170 2-Cl O S-nBu 2171 2-Br O S-nBu 2172 2-CF₃ O S-nBu 2173 2-CH₃ O S-nBu 2174 2-OCH₃ O S-nBu

TABLE 52 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2175 2,6-F₂ O S-nBu 2176 2,6-Cl₂ O S-nBu 2177 2,6-(CH₃)₂ O S-nBu 2178 2-F, 6-Cl O S-nBu 2179 2,3,5-Cl₃ O S-nBu 2180 2-Cl, 6-CH₃ O S-nBu 2181 2-F, 6-CH₃ O S-nBu 2182 2-F O S-iBu 2183 2-Cl O S-iBu 2184 2-Br O S-iBu 2185 2-CF₃ O S-iBu 2186 2-CH₃ O S-iBu 2187 2-OCH₃ O S-iBu 2188 2,6-F₂ O S-iBu 2189 2,6-Cl₂ O S-iBu 2190 2,6-(CH₃)₂ O S-iBu 2191 2-F, 6-Cl O S-iBu 2192 2,3,5-Cl₃ O S-iBu 2193 2-Cl, 6-CH₃ O S-iBu 2194 2-F, 6-CH₃ O S-iBu 2195 2-F O S-Allyl 2196 2-Cl O S-Allyl 2197 2-Br O S-Allyl 2198 2-CF₃ O S-Allyl 2199 2-CH₃ O S-Allyl

TABLE 53 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2200 2-OCH₃ O S-Allyl 2201 2,6-F₂ O S-Allyl 2202 2,6-Cl₂ O S-Allyl 2203 2,6-(CH₃)₂ O S-Allyl 2204 2-F, 6-Cl O S-Allyl 2205 2,3,5-Cl₃ O S-Allyl 220 2-Cl, 6-CH₃ O S-Allyl 2207 2-F, 6-CH₃ O S-Allyl 2208 2-F O SCH₂-Allyl 2209 2-Cl O SCH₂-Allyl 2210 2-Br O SCH₂-Allyl 2211 2-CF₃ O SCH₂-Allyl 2212 2-CH₃ O SCH₂-Allyl 2213 2-OCH₃ O SCH₂-Allyl 2214 2,6-F₂ O SCH₂-Allyl 2215 2,6-Cl₂ O SCH₂-Allyl 2216 2,6-(CH₃)₂ O SCH₂-Allyl 2217 2-F, 6-Cl O SCH₂-Allyl 2218 2,3,5-Cl₃ O SCH₂-Allyl 2219 2-Cl, 6-CH₃ O SCH₂-Allyl 2220 2-F, 6-CH₃ O SCH₂-Allyl 2221 2,6-Cl₂ O cPr 2222 2-CH₃ O cPr 2223 2,6-Cl₂ O OCH₂-cPr 2224 2-CH₃ O OCH₂-cPr

TABLE 54 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2225 2,6-Cl₂ O OCH₂CH₂Cl 2226 2-CH₃ O OCH₂CH₂Cl 2227 2,6-Cl₂ O OCH₂CH₂Ph 2228 2-CH₃ O OCH₂CH₂Ph 2229 2,6-Cl₂ O OCH₂C(Me)=CH₂ 2230 2-CH₃ O OCH₂C(Me)=CH₂

TABLE 55 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2231 2-F S O-Me 2232 2-Cl S O-Me 2233 2-Br S O-Me 2234 2-CF₃ S O-Me 2235 2-CH₃ S O-Me 2236 2-OCH₃ S O-Me 2237 2,6-F₂ S O-Me 2238 2,6-Cl₂ S O-Me 2239 2,6-(CH₃)₂ S O-Me 2240 2-F, 6-Cl S O-Me 2241 2,3,5-Cl₃ S O-Me 2242 2-Cl, 6-CH₃ S O-Me 2243 2-F, 6-CH₃ S O-Me 2244 2-F S O-Et 2245 2-Cl S O-Et 2246 2-Br S O-Et 2247 2-CF₃ S O-Et 2248 2-CH₃ S O-Et 2249 2-OCH₃ S O-Et 2250 2,6-F₂ S O-Et 2251 2,6-Cl₂ S O-Et 2252 2,6-(CH₃)₂ S O-Et 2253 2-F, 6-Cl S O-Et 2254 2,3,5-Cl₃ S O-Et 2255 2-Cl, 6-CH₃ S O-Et

TABLE 56 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2256 2-F, 6-CH₃ S O-Et 2257 2-F S O-nPr 2258 2-Cl S O-nPr 2259 2-Br S O-nPr 2260 2-CF₃ S O-nPr 2261 2-CH₃ S O-nPr 2262 2-OCH₃ S O-nPr 2263 2,6-F₂ S O-nPr 2264 2,6-Cl₂ S O-nPr 2265 2,6-(CH₃)₂ S O-nPr 2266 2-F, 6-Cl S O-nPr 2267 2,3,5-Cl₃ S O-nPr 2268 2-Cl, 6-CH₃ S O-nPr 2269 2-F, 6-CH₃ S O-nPr 2270 2-F S O-nBu 2271 2-Cl S O-nBu 2272 2-Br S O-nBu 2273 2-CF₃ S O-nBu 2274 2-CH₃ S O-nBu 2275 2-OCH₃ S O-nBu 2276 2,6-F₂ S O-nBu 2277 2,6-Cl₂ S O-nBu 2278 2,6-(CH₃)₂ S O-nBu 2279 2-F, 6-Cl S O-nBu 2280 2,3,5-Cl₃ S O-nBu

TABLE 57 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2281 2-Cl, 6-CH₃ S O-nBu 2282 2-F, 6-CH₃ S O-nBu 2283 2-F S O-iBu 2284 2-Cl S O-iBu 2285 2-Br S O-iBu 2286 2-CF₃ S O-iBu 2287 2-CH₃ S O-iBu 2288 2-OCH₃ S O-iBu 2289 2,6-F₂ S O-iBu 2290 2,6-Cl₂ S O-iBu 2291 2,6-(CH₃)₂ S O-iBu 2292 2-F, 6-Cl S O-iBu 2293 2,3,5-Cl₃ S O-iBu 2294 2-Cl, 6-CH₃ S O-iBu 2295 2-F, 6-CH₃ S O-iBu 2296 2-F S O-Allyl 2297 2-Cl S O-Allyl 2298 2-Br S O-Allyl 2299 2-CF₃ S O-Allyl 2300 2-CH₃ S O-Allyl 2301 2-OCH₃ S O-Allyl 2302 2,6-F₂ S O-Allyl 2303 2,6-Cl₂ S O-Allyl 2304 2,6-(CH₃)₂ S O-Allyl 2305 2-F, 6-Cl S O-Allyl

TABLE 58 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2306 2,3,5-Cl₃ S O-Allyl 2307 2-Cl, 6-CH₃ S O-Allyl 2308 2-F, 6-CH₃ S O-Allyl 2309 2-F S OCH₂-Allyl 2310 2-Cl S OCH₂-Allyl 2311 2-Br S OCH₂-Allyl 2312 2-CF₃ S OCH₂-Allyl 2313 2-CH₃ S OCH₂-Allyl 2314 2-OCH₃ S OCH₂-Allyl 2315 2,6-F₂ S OCH₂-Allyl 2316 2,6-Cl₂ S OCH₂-Allyl 2317 2,6-(CH₃)₂ S OCH₂-Allyl 2318 2-F, 6-Cl S OCH₂-Allyl 2319 2,3,5-Cl₃ S OCH₂-Allyl 2320 2-Cl, 6-CH₃ S OCH₂-Allyl 2321 2-F, 6-CH₃ S OCH₂-Allyl 2322 2-F S OCH₂C≡CH 2323 2-Cl S OCH₂C≡CH 2324 2-Br S OCH₂C≡CH 2325 2-CF₃ S OCH₂C≡CH 2326 2-CH₃ S OCH₂C≡CH 2327 2-OCH₃ S OCH₂C≡CH 2328 2,6-F₂ S OCH₂C≡CH 2329 2,6-Cl₂ S OCH₂C≡CH 2330 2,6-(CH₃)₂ S OCH₂C≡CH

TABLE 59 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2331 2-F, 6-Cl S OCH₂C≡CH 2332 2,3,5-Cl₃ S OCH₂C≡CH 2333 2-Cl, 6-CH₃ S OCH₂C≡CH 2334 2-F, 6-CH₃ S OCH₂C≡CH 2335 2-F S OCH₂CH₂C≡CH 2336 2-Cl S OCH₂CH₂C≡CH 2337 2-Br S OCH₂CH₂C≡CH 2338 2-CF₃ S OCH₂CH₂C≡CH 2339 2-CH₃ S OCH₂CH₂C≡CH 2340 2-OCH₃ S OCH₂CH₂C≡CH 2341 2,6-F₂ S OCH₂CH₂C≡CH 2342 2,6-Cl₂ S OCH₂CH₂C≡CH 2343 2,6-(CH₃)₂ S OCH₂CH₂C≡CH 2344 2-F, 6-Cl S OCH₂CH₂C≡CH 2345 2,3,5-Cl₃ S OCH₂CH₂C≡CH 2346 2-Cl, 6-CH₃ S OCH₂CH₂C≡CH 2347 2-F, 6-CH₃ S OCH₂CH₂C≡CH 2348 2-F S OCH₂C≡CCH₃ 2349 2-Cl S OCH₂C≡CCH₃ 2350 2-Br S OCH₂C≡CCH₃ 2351 2-CF₃ S OCH₂C≡CCH₃ 2352 2-CH₃ S OCH₂C≡CCH₃ 2353 2-OCH₃ S OCH₂C≡CCH₃ 2354 2,6-F₂ S OCH₂C≡CCH₃ 2355 2,6-Cl₂ S OCH₂C≡CCH₃

TABLE 60 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2356 2,6-(CH₃)₂ S OCH₂C≡CCH₃ 2357 2-F, 6-Cl S OCH₂C≡CCH₃ 2358 2,3,5-Cl₃ S OCH₂C≡CCH₃ 2359 2-Cl, 6-CH₃ S OCH₂C≡CCH₃ 2360 2-F, 6-CH₃ S OCH₂C≡CCH₃ 2361 2,6-Cl₂ S cPr 2362 2-CH₃ S cPr 2363 2,6-Cl₂ S OCH₂-cPr 2364 2-CH₃ S OCH₂-cPr 2365 2,6-Cl₂ S OCH₂CH₂Cl 2366 2-CH₃ S OCH₂CH₂Cl 2367 2,6-Cl₂ S OCH₂CH₂Ph 2368 2-CH₃ S OCH₂CH₂Ph 2369 2,6-Cl₂ S OCH₂C(Me)=CH₂ 2370 2-CH₃ S OCH₂C(Me)=CH₂ 2371 2-F O Me 2372 2-Cl O Me 2373 2-Br O Me 2374 2-CF₃ O Me 2375 2-CH₃ O Me 2376 2-OCH₃ O Me 2377 2,6-F₂ O Me 2378 2,6-Cl₂ O Me 2379 2,6-(CH₃)₂ O Me 2380 2-F, 6-Cl O Me

TABLE 61 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2381 2,3,5-Cl₃ O Me 2382 2-Cl, 6-CH₃ O Me 2383 2-F, 6-CH₃ O Me 2384 2-F O Et 2385 2-Cl O Et 2386 2-Br O Et 2387 2-CF₃ O Et 2388 2-CH₃ O Et 2389 2-OCH₃ O Et 2390 2,6-F₂ O Et 2391 2,6-Cl₂ O Et 2392 2,6-(CH₃)₂ O Et 2393 2-F, 6-Cl O Et 2394 2,3,5-Cl₃ O Et 2395 2-Cl, 6-CH₃ O Et 2396 2-F, 6-CH₃ O Et 2397 2-F O nPr 2398 2-Cl O nPr 2399 2-Br O nPr 2400 2-CF₃ O nPr 2401 2-CH₃ O nPr 2402 2-OCH₃ O nPr 2403 2,6-F₂ O nPr 2404 2,6-Cl₂ O nPr 2405 2,6-(CH₃)₂ O nPr

TABLE 62 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2406 2-F, 6-Cl O nPr 2407 2,3,5-Cl₃ O nPr 2408 2-Cl, 6-CH₃ O nPr 2409 2-F, 6-CH₃ O nPr 2410 2-F O nBu 2411 2-Cl O nBu 2412 2-Br O nBu 2413 2-CF₃ O nBu 2414 2-CH₃ O nBu 2415 2-OCH₃ O nBu 2416 2,6-F₂ O nBu 2417 2,6-Cl₂ O nBu 2418 2,6-(CH₃)₂ O nBu 2419 2-F, 6-Cl O nBu 2420 2,3,5-Cl₃ O nBu 2421 2-Cl, 6-CH₃ O nBu 2422 2-F, 6-CH₃ O nBu 2423 2-F O nPen 2424 2-Cl O nPen 2425 2-Br O nPen 2426 2-CF₃ O nPen 2427 2-CH₃ O nPen 2428 2-OCH₃ O nPen 2429 2,6-F₂ O nPen 2430 2,6-Cl₂ O nPen

The compounds represented by the formula:

TABLE 63 Compound No. R¹², R²², R³², R⁴², R⁵² Y¹ X¹ 2431 2,6-(CH₃)₂ O nPen 2432 2-F, 6-Cl O nPen 2433 2,3,5-Cl₃ O nPen 2435 2-Cl, 6-CH₃ O nPen

TABLE 64 Compound No. Y¹ X¹ 2436 O Me 2437 O Et 2438 O nPr 2439 O nBu 2440 O nPen 2441 O cPr 2442 O CH₂Ph 2443 O O-Me 2444 O O-Et 2445 O O-nPr 2446 O O-nBu 2447 O O-iBu 2448 O O-Allyl 2449 O OCH₂C≡CH 2450 O OCH₂CH₂C≡CH 2451 O OCH₂C≡CCH₃ 2452 O O-Me 2453 O O-Et 2454 O O-nPr 2455 O O-nBu 2456 O O-iBu 2457 O O-Allyl 2458 O OCH₂C≡CH 2459 O OCH₂CH₂C≡CH 2560 O OCH₂C≡CCH₃

[In the above Tables 1 to 64, Me stands for methyl group, Et for ethyl group, nPr for normal propyl group, iPr for isopropyl group, cPr for cyclopropyl group, nBu for normal butyl group, sBu for secondary butyl group, iBu for isobutyl group, nPen for normal pentyl group, Allyl for 2-propenyl group, and Ph for phenyl group. In case a compound contains an asymmetric carbon atom(s), it includes one of the optical active compounds and their mixtures.]

Melting points of some of the compounds of the present invention are shown below.

Compound 18: 170.3° C.

Compound 31: 160.2° C.

Compound 164: 168.7° C.

Compound 177: 142.3° C.

Compound 281: 150.6° C.

Compound 291: 92.9° C.

Compound 294: 163.3° C.

Compound 327: 111.2° C.

Compound 590: 146.7° C.

Compound 333: 150.9° C.

Compound 359: 132.7° C.

Compound 372: 121.1° C.

Compound 385: 143.7° C.

Compound 586: 148.2° C.

Compound 587: 89.8° C.

¹H-NMR (CDCl₃, TMS) data of some of the present compound are shown below.

Compound 87: 7.15-7.3 (4H), 5.8 (2H), 3.35 (1H), 2.8 (2H), 2.27 (3H), 1.8-2.2 (2H, 1.36 (3H), 1.24 (3H), 1.01 (3H)

Compound 278: 7.16-7.24 (4H), 5.5 (2H, 4.41 (2H), 3.8 (1H), 2.27 (3H), 2.1 (1H, 1.7 (1H), 1.43 (3H), 1.32 (3H), 1.00 (3H)

Compound 878: 7.8-7.9 (3H), 7.46-7.50 (4H), 5.68 (2H), 4.43 (2H), 4.13 (1H), 1.47 (9H)

¹H-NMR (CDCl₃, TMS) data of some of the intermediates A are shown below.

Compound 1014: 7.23-7.46 (4H), 4.86 (2H), 4.15 (1H), 1.55-1.8 (2H), 1.22 (3H), 0.91 (3H) Compound 1020: 7.4 (1H), 7.2-7.3 (2H), 4.83 (2H), 4.15 (1H), 1.55-1.8 (2H), 1.23 (3H), 0.92 (3H)

Compound 1026: 7.80-7.86 (3H), 7.42-7.50 (4H), 4.83 (2H), 4.43 (1H), 1.29 (6H)

Formulation examples of the present compounds are shown below. In the following descriptions of Formulation examples, all “parts” are by weight unless otherwise noted, and the present compounds are indicated by the Compound numbers shown in Tables 1 to 40.

Formulation Example 1

50 parts each of the Compounds 1 to 940, 3 parts of calcium lignin sulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrous silicon oxide were ground and mixed well to obtain wettable powders.

Formulation Example 2

25 parts each of the Compounds 1 to 940, 3 parts of polyoxyethylene sorbitan monooleate, 3 parts of CMC and 69 parts of wet were mixed and water-ground until the particle size of the active ingredient became less than 5 microns to obtain flowables.

Formulation Example 3

2 parts each of the Compounds 1 to 940, 88 parts of kaolin clay and 10 parts of talc were ground and mixed well to obtain powders.

Formulation Example 4

2 parts each of the Compounds 1 to 940, one part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay were ground and mixed well, and the mixture was kneaded well by adding water, then granulated and dried to obtain granules.

Formulation Example 5

20 parts each of the Compounds 1 to 940 and 1.5 part of sorbitan trioleate were mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and the mixture was finely ground (to a particle size of less than 3 microns) by a sand grinder. To this ground mixture was added 40 parts of an aqueous solution containing 0.05 part of xanthane gum and 0.1 part of aluminum magnesium silicate, followed by further addition of 10 parts of propylene glycol and mixing by stirring to obtain 20% water suspensions.

Usefulness of the present compounds as a plant disease controlling agent is illustrated by a Test Example. The present compounds used are indicated by the Compound numbers shown in Tables 1 to 40.

The controlling effect of the present compounds against plant diseases was determined by observing with the naked eye the areal ratio of the morbid spots on the test plants at the time of examination and comparing the total area of spots in the no-treatment (control) section with that in the compound-treated section.

Test Example: Test of Controlling Effect (Prophylactic Effect) Against Botrytis cinerea of Cucumber

Seeds of cucumber (variety: Sagami hanpaku) were sown in the plastic pots packed with sandy loam and let sprout and grow in a hothouse for 12 days. Wettable powders were prepared with the Compounds 18, 31, 87, 151, 164, 177, 190, 203, 216, 229, 242, 255, 278, 281, 294, 327, 330, 333, 346, 356, 359, 372, 385, 408, 411, 463, 499, (+)-499, (−)-499, 502, (+)-502, (−)-502, 551, 574, 578, 582, 595 and 621 according to the method of Formulation Example 1, and each of these wettable powders was diluted with water to a prescribed concentration (200 ppm). Each of the thus prepared solutions was sprayed to the stalks and leaves of cucumber so that the solution would adhere sufficiently to the leave surfaces. The sprayed plants were air-dried, and a PDA medium containing hyphae of the fungi of Botrytis cinerea of cucumber was placed on the cucumber leave surfaces. The test plastic pots were placed under a humid environment of 10° C. for 4 days, and then the controlling effect of the compounds against Botrytis cinerea of cucumber was examined. The result showed that the morbid spot area on the plants in the compound-treated section was less than 10% of that on the plants in the non-treatment section.

EFFECT OF THE INVENTION

The compounds of the present invention have excellent controlling effect against plant diseases. 

What is claimed is:
 1. The pyrazolinone derivatives represented by the formula [I]:

wherein R¹, R², R³, R⁴ and R⁵ may be identical or different and represent independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyl group, an alkoxyalkyl group, an alkoxyalkoxyl group, a haloalkoxyl group, an alkylthio group, a haloalkylthio group, a cyano group, a nitro group, an optionally substituted phenyl group or an optionally substituted phenoxyl group, or adjacent two of R¹, R², R³, R⁴ and R⁵ are combined at the ends to represent a group of the formula CH═CH—CH═CH, a methylenedioxy group which may be substituted with a halogen atom or an alkylene group which may contain one oxygen atom and may be substituted with an alkyl group; R⁶ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group or an optionally substituted alicyclic hydrocarbon group; X represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group, an optionally substituted alkoxyl group, an optionally substituted alkenyloxy group, an optionally substituted alkynyloxy group, an optionally substituted phenoxyl group, an optionally substituted alkylthio group, an optionally substituted alkenylthio group, an optionally substituted alkynylthio group, an optionally substituted phenylthio group or an optionally substituted alicyclic hydrocarbon group; and Y represents an oxygen atom or a sulfur atom.
 2. The pyrazolinone derivatives according to claim 1, wherein in the formula [I], R¹, R², R³, R⁴ and R⁵ are identical or different and represent independently a hydrogen atom, a halogen atom, a C1-C5 alkyl group, a C1-C5 haloalkyl group, a C1-C5 alkoxyl group, a C1-C3 alkoxy C1-C3 alkyl group, a C1-C3 alkoxy C1-C3 alkoxyl group, a C1-C5 haloalkoxyl group, a C1-C5 alkylthio group, a C1-C5 haloalkylthio group, a cyano group, a nitro group, or a phenyl or phenoxyl group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups, or adjacent two of R¹, R², R³, R⁴ and R⁵ are combined at the ends to represent a group of the formula CH═CH—CH═CH, a methylenedioxy group which may be substituted with a halogen atom, a trimethylene group, a tetramethylene group, a group represented by the formula OCH₂CH₂ or a group represented by the formula OCH₂CH (CH₃); R⁶ represents a C1-C10 alkyl group, a C3-C10 alkenyl group, a C3-C10 alkynyl group, a C1-C10 haloalkyl group, a C3-C10 haloalkenyl group, a C3-C10 haloalkynyl group, a C1-C5 alkoxy C1-C5 alkyl group, a C1-C5 alkylthio C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 haloalkyl group, a C1-C5 haloalkylthio C1-C5 alkyl group, a C1-C5 haloalkylthlo C1-C5 haloalkyl group, a cyano C1-C5 alkyl group, a cyano C1-C5 haloalkyl group, a C1-C5 alkoxycarbonyl C1-C5 alkyl group, a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a C1-C5 alkyl group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a phenyl or C7-C17 aralkyl group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups; X represents a C1-C10 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a C1-C10 haloalkyl group, a C2-C10 haloalkynyl group, a C2-C10 haloalkenyl group, a C1-C5 alkoxy C1-C5 alkyl group, a C1-C5 alkylthio C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 haloalkyl group, a C1-C5 haloalkylthio C1-C5 alkyl group, a C1-C5 haloalkylthio C1-C5 haloalkyl group, a cyano C1-C5 alkyl group, a cyano C1-C5 haloalkyl group, a C1-C5 alkyl group substituted with a C1-C5 alkoxycarbonyl group, a C1-C5 alkyl group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a C1-C10 alkoxyl group, a C2-C10 alkenyloxy group, a C2-C10 alkynyloxy group, a C1-C10 haloalkoxyl group, a C2-C10 haloalkenyloxy group, a C2-C10 haloalkynyloxy group, C1-C5 alkoxy C1-C5 alkoxyl group, a C1-C5 alkylthio C1-C5 alkoxyl group, a C1-C5 haloalkoxy C1-C5 alkoxyl group, a C1-C5 haloalkoxy C1-C5 haloalkoxyl group, a C1-C5 haloalkylthio C1-C5 alkoxyl group, a C1-C5 haloalkylthio C1-C5 haloalkoxyl group, a cyano C1-C5 alkoxyl group, a C1-C5 alkoxycarbonyl C1-C5 alkoxyl group, a C1-C5 alkoxyl group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a phenyl group, C7-C17 aralkyl group, phenoxyl group, C7-C17 aralkyloxy group, phenylthio group or C7-C17 aralkylthio group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxy C1-C5 haloalkylthio groups and cyano groups, a C1-C10 alkylthio group, a C2-C10 alkenylthio group, a C2-C10 alkynylthio group, a Cl-C10 haloalkylthio group, a C2-C10 haloalkynylthio group, a C2-C10 haloalkenylthio group, a C1-C5 alkoxy C1-C5 alkylthio group, a C1-C5 alkylthio C1-C5 alkylthio group, a C1-C5 haloalkoxy C1-C5 alkylthio group, a C1-C5 haloalkoxy C1-C5 haloalkylthio group, a C1-C5 haloalkylthio C1-C5 alkylthio group, a C1-C5 haloalkylthio C1-C5 haloalkylthio group, a cyano C1-C5 alkylthio group, a C1-C5 alkoxycarbonyl C1-C5 alkylthio group, a C1-C5 alkylthio group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, or a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds.
 3. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], R¹, R², R³, R⁴ and R⁵ are identical or different and represent independently a hydrogen atom, a halogen atom, a C1-C5 alkyl group, a C1-C5 haloalkyl group or a C1-C5 alkoxyl group, or adjacent two of R¹, R², R³, R⁴ and R⁵ are combined at the ends to represent a group of the formula CH═CH—CH═CH.
 4. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], R³, R⁴ and R⁵ are a hydrogen atom.
 5. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], R¹ is a halogen atom or a methyl group which may be substituted with a halogen atom, and R² is a hydrogen atom, a halogen atom or a methyl group which may be substituted with a halogen atom.
 6. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], R⁶ is a C1-C10 alkyl group, a C3-C10 alkenyl group, a C3-C10 alkynyl group, a C1-C10 haloalkyl group, a C3-C10 haloalkenyl group, a C3-C10 haloalkynyl group, a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, or a C1-C5 alkyl group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds.
 7. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], X is a C1-C10 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a C1-C10 haloalkyl group, a C2-C10 haloalkenyl group, a C2-C10 haloalkynyl group, a phenyl group, phenoxyl group or phenylthio group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, a C1-C5 haloalkylthio groups and cyano groups, a C1-C10 alkoxyl group, a C2-C10 alkenyloxy group, a C2-C10 alkynyloxy group, a C1-C10 haloalkoxyl group, C2-C10 haloalkenyloxy group, a C2-C10 haloalkynyloxy group, a C1-C10 alkylthio group, a C2-C10 alkenylthio group, a C2-C10 alkynylthio group, a C1-C10 haloalkylthio group, a C2-C10 haloalkenylthio group or a C2-C10 haloalkynylthio group, or a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom or may contain unsaturated bonds.
 8. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], X is a methylthio group, an ethylthio group, a propylthio group or a 2-propenylthio group.
 9. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], R⁶ is an isopropyl group, a 1-methylbutyl group or a sec-butyl group.
 10. The pyrazolinone derivatives according to claim 1 or 2, wherein in the formula [I], Y is an oxygen atom.
 11. A plant disease controlling agent characterized in that it contains a pyrazolinone derivative set forth in claim 1 or 2 as an active ingredient.
 12. The pyrazolinone compounds represented by the formula [II]:

wherein R¹¹ and R²¹ may be identical or different and represent independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyl group, an alkoxyalkyl group, an alkoxyalkoxyl group, a haloalkoxyl group, an alkylthio group, a haloalkylthio group, a cyano group, a nitro group, an optionally substituted phenyl group or an optionally substituted phenoxyl group, R³¹, R⁴¹ and R⁵¹ represent a hydrogen atom, R⁶¹ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group or an optionally substituted alicyclic hydrocarbon group.
 13. The pyrazolinone compounds according to claim 12, wherein in the formula [II], R¹¹ and R²¹ are identical or different and represent independently a hydrogen atom, a halogen atom, a C1-C5 alkyl group, a C1-C5 haloalkyl group, a C1-C5 alkoxyl group, a C1-C3 alkoxy C1-C3 alkyl group, a C1-C3 alkoxy C1-C3 alkoxyl group, a C1-C5 haloalkoxyl group, a C1-C5 alkylthio group, a C1-C5 haloalkylthio group, a cyano group, a nitro group, a phenyl group or phenoxyl group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups, R⁶¹ is a C1-C10 alkyl group, a C3-C10 alkenyl group, a C3-C10 alkynyl group, a C1-C10 haloalkyl group, a C3-C10 haloalkenyl group, a C3-C10 haloalkynyl group, a C1-C5 alkoxy C1-C5 alkyl group, a C1-C5 alkylthio C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 haloalkyl group, a C1-C5 haloalkylthio C1-C5 alkyl group, a C1-C5 haloalkylthio C1-C5 haloalkyl group, a cyano C1-C5 alkyl group, a cyano C1-C5 haloalkyl group, a C1-C5 alkoxycarbonyl C1-C5 alkyl group, a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a C1-C5 alkyl group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, or a C7-C17 aralkyl group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups.
 14. The pyrazolinone compounds according to claim 12 or 13, wherein in the formula [II], R¹¹ and R²¹ are identical or different and represent independently a hydrogen atom, a halogen atom, a C1-C5 alkyl group, a C1-C5 haloalkyl group or a C1-C5 alkoxyl group.
 15. The pyrazolinone compounds according to claim 12 or 13, wherein in the formula [II], R¹¹ is a halogen atom or a methyl group which may be substituted with a halogen atom, and R²¹ is a hydrogen atom, a halogen atom or a methyl group which may be substituted with a halogen atom.
 16. The pyrazolinone compounds according to claim 12 or 13, wherein in the formula [II], R⁶¹ is an isopropyl group, a 1-methylbutyl group or a sec-butyl group.
 17. The pyrazolinone compounds represented by the formula [III]:

wherein R¹², R²², R³², R⁴² and R⁵² may be identical or different and represent independently a hydrogen atom, a halogen atom, an alkyl group, a haloalkyl group, an alkoxyl group, an alkoxyalkyl group, an alkoxyalkoxyl group, a haloalkoxyl group, an alkylthio group, a haloalkylthio group, a cyano group, a nitro group, an optionally substituted phenyl group or an optionally substituted phenoxyl group, or adjacent two of R¹², R²², R³², R⁴² and R⁵² are combined at the ends to represent a group of the formula CH═CH—CH═CH, a methylenedioxy group which may be substituted with a halogen atom or an alkylene group which may contain one oxygen atom and may be substituted with an alkyl group; X¹ represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted phenyl group, an optionally substituted alkoxyl group, an optionally substituted alkenyloxy group, an optionally substituted alkynyloxy group, an optionally substituted phenoxyl group, an optionally substituted alkylthio group, an optionally substituted alkenylthio group, an optionally substituted alkynylthio group, an optionally substituted phenylthio group or an optionally substituted alicyclic hydrocarbon group; and Y¹ represents an oxygen atom or a sulfur atom.
 18. The pyrazolinone compounds according to claim 17, wherein in the formula [III], R¹², R²², R³², R⁴² and R⁵² are identical or different and represent independently a hydrogen atom, a halogen atom, a C1-C5 alkyl group, a C1-C5 haloalkyl group, a C1-C5 alkoxyl group, a C1-C3 alkoxy C1-C3 alkyl group, a C1-C3 alkoxy C1-C3 alkoxyl group, a C1-C5 haloalkoxyl group, a C1-C5 alkylthio group, C1-C5 haloalkylthio group, a cyano group, a nitro group or a phenyl or phenoxyl group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups, or adjacent two of R¹², R²², R³², R⁴² and R⁵² are combined at the ends to represent a group of the formula CH═CH—CH═CH, a methylenedioxy group (which may be substituted with a halogen atom), a trimethylene group, a tetramethylene group, a group represented by the formula OCH₂CH₂ or a group represented by the formula OCH₂CH(CH₃); and X¹ represents a C1-C10 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a C1-C10 haloalkyl group, a C2-C10 haloalkenyl group, a C2-C10 haloalknyl group, a C1-C5 alkoxy C1-C5 alkyl group, a C1-C5 alkylthio C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 alkyl group, a C1-C5 haloalkoxy C1-C5 haloalkyl group, a C1-C5 haloalkylthio C1-C5 alkyl group, a C1-C5 haloalkylthio C1-C5 haloalkyl group, a cyano C1-C5 alkyl group, a cyano C1-C5 haloalkyl group, a C1-C5 alkyl group substituted with a C1-C5 alkoxycarbonyl group, a C1-C5 alkyl group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a phenyl, C7-C17 aralkyl, phenoxyl, C7-C17 aralkyloxy, phenylthio or C7-C17 aralkylthio group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups, a C1-C10 alkoxyl group, a C2-C10 alkenyloxy group, a C2-C10 alkynyloxy group, a C1-C10 haloalkoxyl group, a C2-C10 haloalkenyloxy group, a C2-C10 haloalkynyloxy group, a C1-C5 alkoxy C1-C5 alkoxyl group, a C1-C5 alkylthio C1-C5 alkoxyl group, a C1-C5 haloalkoxy C1-C5 alkoxyl group, a C1-C5 haloalkoxy C1-C5 haloalkoxyl group, a C1-C5 haloalkylthio C1-C5 alkoxyl group, a C1-C5 haloalkylthio C1-C5 haloalkoxyl group, a cyano C1-C5 alkoxyl group, a C1-C5 alkoxycarbonyl C1-C5 alkoxyl group, a C1-C5 alkoxyl or C1-C5 alkylthio group substituted with a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds, a C1-C10 alkylthio group, a C2-C10 alkenylthio group, a C2-C10 alkynylthio group, a C1-C10 haloalkylthio group, a C2-C10 haloalkenylthio group, a C2-C10 haloalkynylthio group, a C1-C5 alkoxy C1-C5 alkylthio group, a C1-C5 alkylthio C1-C5 alkylthio group, a C1-C5 haloalkoxy C1-C5 alkylthio group, a C1-C5 haloalkoxy C1-C5 haloalkylthio group, a C1-C5 haloalkylthio C1-C5 alkylthio group, a C1-C5 haloalkylthio C1-C5 haloalkylthio group, a cyano C1-C5 alkylthio group, a C1-C5 alkoxycarbonyl C1-C5 alkylthio group or a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds.
 19. The pyrazolinone compounds according to claim 17 or 18, wherein in the formula [III], R¹², R²², R³², R⁴² and R⁵² are identical or different and represent independently a hydrogen atom, a halogen atom, a C1-C5 alkyl group, a C1-C5 haloalkyl group or a C1-C5 alkoxyl group, or adjacent two of R¹², R²², R³², R⁴² and R⁵² are combined at the ends to represent a group of the formula CH═CH—CH═CH.
 20. The pyrazolinone compounds according to claim 17 or 18, wherein in the formula [III], R³², R⁴² and R⁵² are a hydrogen atom.
 21. The pyrazolinone compounds according to claim 17 or 18, wherein in the formula [III], R¹² is a halogen atom or a methyl group which may be substituted with a halogen atom, and R²² is a hydrogen atom, a halogen atom or a methyl group which may be substituted with a halogen atom.
 22. The pyrazolinone compounds according to claim 17 or 18, wherein in the formula [III], X¹ is a C1-C10 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a C1-C10 haloalkyl group, a C2-C10 haloalkenyl group, a C2-C10 haloalkynyl group, a C1-C10 alkoxyl group, a C1-C10 haloalkoxyl group, a C2-C10 alkenyloxy group, a C2-C10 haloalkenyloxy group, a C2-C10 alkynyloxy group, a C2-C10 haloalkynyloxy group, a phenyl, phenoxyl or phenylthio group which may be substituted with at least one group selected from the group consisting of halogen atoms, C1-C5 alkyl groups, C1-C5 alkoxyl groups, C1-C5 alkylthio groups, C1-C5 haloalkyl groups, C1-C5 haloalkoxyl groups, C1-C5 haloalkylthio groups and cyano groups, a C1-C10 alkylthio group, a C2-C10 alkenylthio group, a C2-C10 alkynylthio group, a C1-C10 haloalkylthio group, a C2-C10 haloalkenylthio group, C2-C10 haloalkynylthio group or a C3-C8 alicyclic hydrocarbon group which may be substituted with a halogen atom and may contain unsaturated bonds.
 23. The pyrazolinone compounds according to claim 17, or 18, wherein in the formula [III], X¹ is a methylthio group, an ethylthio group, a propylthio group or a 2-propenylthio group.
 24. The pyrazolinone compounds according to claim 17, or 18, wherein in the formula [III], Y¹ is an oxygen atom.
 25. A method for controlling plant diseases which comprises applying a pyrazolinone derivative of the formula [I] set forth in claim 1 as an active ingredient to a place where the germs of plant diseases propagate. 